The Wound&#X002f;Burn Guidelines &#X2013

Home , Bromelain (pharmacology), Cadexomer iodine

doi: 10.1111/1346-8138.13288 Journal of Dermatology 2016; : 1–22

GUIDELINE The wound/burn guidelines – 6: Guidelines for the management of burns Yuichiro YOSHINO,1 Mikio OHTSUKA,2 Masakazu KAWAGUCHI,3 Keisuke SAKAI,4 Akira HASHIMOTO,5 Masahiro HAYASHI,3 Naoki MADOKORO,6 Yoshihide ASANO,7 Masatoshi ABE,8 Takayuki ISHII,9 Taiki ISEI,10 Takaaki ITO,11 Yuji INOUE,12 Shinichi IMAFUKU,13 Ryokichi IRISAWA,14 Masaki OHTSUKA,15 Fumihide OGAWA,16 Takafumi KADONO,7 Tamihiro KAWAKAMI,17 Ryuichi KUKINO,18 Takeshi KONO,19 Masanari KODERA,20 Masakazu TAKAHARA,21 Miki TANIOKA,22 Takeshi NAKANISHI,23 Yasuhiro NAKAMURA,24 Minoru HASEGAWA,9 Manabu FUJIMOTO,9 Hiroshi FUJIWARA,25 Takeo MAEKAWA,26 Koma MATSUO,27 Osamu YAMASAKI,15 Andres LE PAVOUX,28 Takao TACHIBANA,29 Hironobu IHN,12 The Wound/Burn Guidelines Committee 1Department of Dermatology, Japanese Red Cross Kumamoto Hospital, Kumamoto, 2Department of Dermatology, Fukushima Medical University, Fukushima, 3Department of Dermatology, Yamagata University Faculty of Medicine, Yamagata, 4Intensive Care Unit, Kumamoto University Hospital, Kumamoto, 5Department of Dermatology, Tohoku University Graduate School of Medicine, Miyagi, 6Department of Dermatology, Mazda Hospital, Hiroshima, 7Department of Dermatology, Faculty of Medicine,University of Tokyo, Tokyo, 8Department of Dermatology, Gunma University Graduate School of Medicine, Gunma, 9Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, 10Department of Dermatology, Kansai Medical University, Osaka, 11Department of Dermatology, Hyogo College of Medicine, Hyogo, 12Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, 13Department of Dermatology, Faculty of Medicine, Fukuoka University, Fukuoka, 14Department of Dermatology, Tokyo Medical University, Tokyo, 15Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, 16Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 17Department of Dermatology, St. Marianna University School of Medicine, Kanagawa, 18Department of Dermatology, NTT Medical Center Tokyo, 19Department of Dermatology, Nippon Medical School, Tokyo, 20Department of Dermatology, Japan Community Health Care Organization Chukyo Hospital, Aichi, 21Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 22Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, 23Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, 24Department of Dermatology, University of Tsukuba, Ibaraki, 25Department of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 26Department of Dermatology, Jichi Medical University, Tochigi, 27Department of Dermatology, The Jikei University School of Medicine, Tokyo, 28Ichige Dermatology Clinic, Ibaraki, 29Department of Dermatology, Osaka Red Cross Hospital, Osaka, Japan

ABSTRACT Burns are a common type of skin injury encountered at all levels of medical facilities from private clinics to core hospitals. Minor burns heal by topical treatment alone, but moderate to severe burns require systemic management, and skin grafting is often necessary also for topical treatment. Inappropriate initial treatment or delay of initial treatment may exert adverse effects on the subsequent treatment and course. Therefore, accurate evaluation of the severity and initiation of appropriate treatment are necessary. The Guidelines for the Management of Burn Injuries were issued in March 2009 from the Japanese Society for Burn Injuries as guidelines concerning burns, but they were focused on the treatment for extensive and severe burns in the acute period. Therefore, we prepared guidelines intended to support the appropriate diagnosis and initial treatment for patients with burns that are commonly encountered including minor as well as moderate and severe cases. Because of this intention of the present guidelines, there is no recommendation of individual surgical procedures. Key words: burn index, deep burn, deep dermal burn, epidermal burn, superﬁcial dermal burn.

Correspondence: Hironobu Ihn, M.D., Ph.D., Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. Email: [email protected] This is the secondary English version of the original Japanese manuscript for The wound/burn guidelines – 6: Guidelines for the management of burns published in the Japanese Journal of Dermatology 2011; 121(14): 3279–3306. Received 3 December 2015; accepted 4 December 2015.

guide.medlive.cn Y. Yoshino et al.

BACKGROUND OF THE DRAFTING OF THE COLLECTION OF EVIDENCE GUIDELINES FOR THE MANAGEMENT OF BURNS Databases used: Medline, PubMed, Japana Centra Revuo Medicina Web and Cochrane Database of Systematic Reviews of ALL EBM Reviews. References obtained by manual search Burns are a common type of skin injury encountered at all of each member were also added. levels of medical facilities from private clinics to core hospitals. Search period: The published work that could be searched Minor burns heal by topical treatment alone, but moderate to between January 1980 and December 2008 was reviewed. severe burns require systemic management, and skin grafting Recent published work of importance was added when consid- is often necessary also for topical treatment. Inappropriate ini- ered appropriate. tial treatment or delay of initial treatment may exert adverse Adoption criteria: Priority was placed on systematic reviews effects on the subsequent treatment and course. Therefore, of randomized controlled trials (RCT) and papers on individual accurate evaluation of the severity and initiation of appropriate RCT. If they were not available, papers on cohort studies and treatment are necessary. case–control studies were adopted. Although some papers on To the present, the Guidelines for the Management of Burn case series studies were also used as references, the pub- Injuries were issued in March 2009 from the Japanese Society lished work on basic experiments was excluded. for Burn Injuries as guidelines concerning burns, but they were focused on the treatment of extensive and severe burns in the acute period. Therefore, we prepared guidelines intended to CRITERIA FOR THE DETERMINATION OF THE support the appropriate diagnosis and initial treatment of EVIDENCE AND RECOMMENDATION LEVELS patients with burns that are commonly encountered including The criteria adopted in the Guidelines for the Diagnosis and minor as well as moderate and severe cases. Because of this Treatment of Malignant Tumors edited by the Japanese intention of the present guidelines, there is no recommendation Dermatological Association mentioned below were used as of individual surgical procedures. references. Evidence levels: POSITION OF THE GUIDELINES FOR THE MANAGEMENT OF BURNS I Systematic reviews/meta-analyses. II One or more RCT. The Wound/Burn Guidelines Committee consists of members III Non-RCT (including before/after comparative studies commissioned by the Board of Directors of the Japanese Der- with statistical analysis). matological Association. It held several meetings and evalua- IVa Analytical epidemiological studies (cohort studies). tions in writing since October 2008 and drafted the Guidelines IVb Analytical epidemiological studies (case–control stud- for the Management of Burns by taking opinions of the Scien- ies/cross-sectional studies). tific Committee and Board of Directors of the Japanese Der- V Descriptive studies (case reports and case series stud- matological Association into consideration. The present ies). guidelines show the current standards of the treatment for VI Opinions of special committees and individual experts. burns in Japan. However, as individual patients vary in the background including underlying diseases, severity of symp- Recommendation levels: toms and complications, the physicians who conduct the diag- A Strongly recommended (there is at least one piece of nosis and treatment should determine the therapeutic level I or good level II evidence indicating the effec- approaches together with the patients, so the contents of their tiveness). decisions are not required to be in complete agreement with B Recommended (there is at least one piece of inferior the present guidelines. Also, the guidelines are not relevant for level II, good level III or very good level IV evidence). citation in lawsuits. C1 Recommended as an option despite the lack of good evidence (there is inferior level III–IV evidence, several SPONSORS AND CONFLICTS OF INTEREST pieces of good level V evidence or level VI evidence endorsed by the committee). All cost needed for drafting the present guidelines has been C2 (Presently) not recommendable due to the lack of borne by the Japanese Dermatological Association, and no sufficient evidence (there is no evidence indicating fund has been received from particular organizations, enter- effectiveness or there is evidence indicating ineffec- prises, pharmaceutical companies and so forth. If any mem- tiveness). bers of the committee have been involved in the development D Disrecommended (there is good evidence indicating of particular related drugs and so forth, they were excluded ineffectiveness or harmfulness). from the evaluation of the recommendation levels of the treatments in question. Each member of the committee has no The recommendation levels mentioned in the text are not other conflict of interest to disclose on drafting the present necessarily in agreement with the above, because they were guidelines. determined at some points according to consensus of the

guide.medlive.cn The wound/burn guidelines – 6

committee (by showing evidence levels) in consideration of the “Topical agents”: Drugs applied through the skin or directly international lack of evidence concerning the diagnosis and to skin lesions for topical treatment. Prepared by compounding treatment of the conditions in question, inappropriateness of various active components with a base. directly applying overseas evidence to Japan and practicality “Dressing materials”: Modern wound-dressing materials of the guidelines. aimed to create a moist environment around wounds. Conven- tional sterilized gauze is excluded. REVIEWS BEFORE DISCLOSURE “Wound-dressing materials”: Wound-dressing materials are divided into dressing materials (modern wound-dressing mate- Prior to the disclosure of the guidelines, progresses in rials) and medical materials including gauze (classic wound- drafting were presented at the Annual Meetings of the Japa- dressing materials). The former are medical materials that pro- nese Dermatological Association from 2008 to 2011, opinions vide an optimal environment for wound healing and must be were invited from the association members and necessary used selectively depending on the condition of the wound and revisions were made. Also, the drafts were distributed amount of exudates. The latter allow drying of the wound and to representatives, who were considered to be typical cannot maintain a moist environment if effusion is insufficient. prospective users of the guidelines, their opinions were Wound-dressing materials cover the wound, retain moisture collected and summarized, and the results were reflected in and provide an optimal environment for wound healing. Medi- the drafts. cal materials other than conventional gauze may be called wound-dressing materials or dressing materials. UPDATING POLICIES “Wound bed preparation”: Management of the wound surface environment to promote wound healing. Specifically, The present guidelines will be updated in 3–5 years. However, necrotic tissues are removed, bacterial load is reduced, drying if partial updating becomes necessary, update information is of the wound is prevented, excessive effusion is controlled, presented on the website of the Japanese Dermatological and pockets and wound margins are treated. Association when appropriate. “TIME”: Practical principles of wound bed preparation based on the concept of evaluating factors that prevent wound TERMINOLOGY healing from the viewpoints of tissue (T), infection or inflammation (I), moisture (M) and wound edge (E), and using the results “First-degree burn”: Epidermal burn that shows only reddening for treatment and care. of the injured area and cures without scars. “Moist wound healing”: Maintaining the wound surface in a “Second-degree burn”: Usually classified into two types moist environment. This retains multinucleated leukocytes, according to the depth. macrophages, enzymes and cell growth factors contained in Superficial dermal burn (SDB): A burn that forms a blister. effusion on the wound surface. Such an environment promotes The dermis at the floor of the blister is red. Usually cures autolysis and removal of necrotic tissues and does not interfere after epithelialization in 1–2 weeks. Generally leaves no with cell migration. hypertrophic scar. Deep dermal burn (DDB): A burn that forms a blister. The dermis at the floor of the blister is white and anemic. The DIAGNOSTIC AND THERAPEUTIC injury requires 3–4 weeks until cure by epithelialization but is ALGORITHMS likely to leave hypertrophic scar or cicatricial keloid. Diagnostic and therapeutic algorithms were prepared on the “Third-degree burn”: Deep burn causing necrosis of the full assumption that the severity evaluation is performed first when thickness of the skin. It includes burns with a white or brown a burn patient is encountered. Figure 1 shows the diagnostic leather-like appearance and burns with completely charred skin. and therapeutic algorithms and clinical questions (CQ). Because epithelialization progresses only from the margins of the – injury, 1 3 months or longer is needed until cure, and hyper- “SEVERITY EVALUATION”: trophic scar or cicatricial contracture occurs without skin grafting. CQ1: WHAT IS RECOMMENDED AS A “Burn index (BI)”: An index devised by representing the 9 METHOD FOR ESTIMATING THE DEPTH OF severity of burns. Calculated as 1/2 area of second-degree BURNS? burn (%) + area of third-degree burn (%). A BI of 10–15 or higher is considered severe. Remarks on recommendation: A classification based on clinical “Prognostic burn index (PBI)”: An index representing the symptoms is recommended as a method for estimating the severity of burns. Calculated as age (years) + BI. depth of burns (B). “Inhalation injury (burn)”: Damage of the pharyngeal/laryn- For more precise estimation, the use of laser Doppler geal or tracheal/bronchial mucosa or the pulmonary alveoli flowmetry or video microscopy with the classification based on caused by inhalation of smoke, high-pressure vapor and toxic clinical symptoms is recommended as an option (C1). gas due to fire or explosion. Recommendation level: B and C1. “Total body surface area (TBSA)”: Total body surface area. Comments:

guide.medlive.cn Y. Yoshino et al.

Burn injury

Severity evaluation CQ 1~4, CQ10

Moderate,Severe Minor over 15 over 2 less than 15 Inhalation injury less than 2 Burns of face, hands, feet or genitalia Burns complicated by fracture or major soft tissue injury

Infection control Systemic management CQ15 19 fluid resuscitation ( CQ 5~9) Burn area: over 15 (Adults) , over10 (Children) Evaluation and management of specific anatomical burn(eyes, airway etc.) CQ10 14 Infection control CQ15 19

Topical treatments (CQ 20~24) The escharotomies and fasciotomies should be considered for the extensive burns, if there are disorder of circulation in extremities or chest movement. In the cases which would need more than 2 weeks until healing, the surgical treatments should be considered.

No Yes Healing Surgical indications

Surgical therapy

Figure 1. Diagnostic and therapeutic algorithms for burn injury.

The method for the estimation of the depth based on clinical Table 1. Method for the estimation of the depth based on findings (Table 1) is regarded as a reference for depth evalu- clinical findings ation and is in wide clinical use, but as there is only a case Depth Clinical findings report,1 the evidence level is V. However, the recommenda- Epidermal burn Redness (+), pain (+) tion level was set at B, because it requires no particular Superficial Redness (+), blisters (+), pain (+), instrument and is widely accepted. Regarding the method dermal burn Blanches with pressure for the estimation of the depth of burns, there is a prospec- Deep dermal burn Variable color (patchy to cheesy white to red), blisters (+), pain tive non-randomized comparative trial comparing laser Dop- (+/À)to(À), pler flowmetry and video microscopy,2 and the evidence Does not blanche with pressure level is III. The sensitivity for the detection of superficial par- Deep burn Waxy white to leathery gray to tial-thickness burn, compared in 27 patients within 72 h charred and black, blister (À), pain (À) after injury, was 100% by both methods, and the lesions

guide.medlive.cn The wound/burn guidelines – 6

diagnosed as superficial partial-thickness burn cured within Comments: 3 weeks. In addition, there are analytical epidemiological Concerning the methods to estimate the burned area using the studies and case reports using laser Doppler flowmetry and rule of nines, rule of fives, and Lung and Browder Chart, there – video microscopy.3 5 are only expert opinions,6–8 and the evidence level is VI. How- ever, the recommendation level was set at B, because they are in wide clinical use, and in consideration of the historical back- REFERENCES ground. Regarding the palm method, there are some differences in the method to determine the reference TBSA, but 1 Heimbach D, Engrav L, Grube B, Marvin J. Burn depth: a review. World J Surg 1992; 16:10–15. (evidence level V). there are analytical epidemiological studies that the palm area, 2 McGill DJ, Sorensen K, MacKay IR, Taggart I, Watson SB. Assess- corresponding to approximately 1% (range, 0.7–0.95%) of the – ment of burn depth: a prospective, blinded comparison of laser TBSA, is useful for the estimation of the burned area,9 11 and Doppler imaging and videomicroscopy. Burns 2007; 33: 833–842. the evidence level is IVa. However, the recommendation level (evidence level III). was set at B, because it is clinically applicable and practical. 3 Pape SA, Skouras CA, Byrne PO. An audit of the use of laser Dop- pler imaging (LDI) in the assessment of burns of intermediate See Figure 2 for the rule of nines, rule of fives, and Lund depth. Burns 2001; 27: 233–239. (evidence level IVa). and Browder Chart. The palm method estimates the burned 4 Yeong EK, Mann R, Goldberg M, Engrav L, Heimbach D. Improved area by assuming the area of the palm to be approximately accuracy of burn wound assessment using laser Doppler. J 1% of the TBSA in adults. Trauma 1996; 40: 956–961. (evidence level IVa). 5 Isono N, Nakazawa H, Nozaki M, Sasaki K. Early assessment of second degree burn depth by means of video microscope. JJ Burn Inj 1998; 24:11–18. (evidence level V). REFERENCES

6 Wallace AB. The exposure treatment of burns. Lancet 1951; 1: CQ2: WHAT IS RECOMMENDED AS A 501–504. (evidence level VI). METHOD FOR ESTIMATING THE BURNED 7 Blocker TG. Local and general treatment of acute extensive burns: AREA? the open-air regime. Lancet 1951; 1: 498–501. (evidence level VI) 8 Lund CC, Browder NC. The estimation of areas of burns. Surg – Remarks on recommendation: As methods to estimate the Gynecol Obste 1944; 79: 352 358. (evidence level VI). 9 Sheridan RL, Petras L, Basha G et al. Planimetry study of the per- burned area, the use of the rule of nines, rule of ﬁves, and cent of body surface represented by the hand and palm: sizing Lund and Browder Chart is recommended (B). irregular burns is more accurately done with the palm. J Burn Care The palm method is recommended as a method for local Rehabil 1995; 16: 605–606. (evidence level IVa). estimation of the burned area (B). 10 Perry RJ, Moore CA, Morgan BD, Plummer DL. Determining the Recommendation level: B. approximate area of a burn: an inconsistency investigated and re- evaluated. BMJ 1996; 312: 1338. (evidence level IVa).

Figure 2. Calculation of burn area.

guide.medlive.cn Y. Yoshino et al.

11 Nagel TR, Schunk JE. Using the hand to estimate the surface area Comments: – of a burn in children. Pediatr Emerg Care 1997; 13: 254 255. (evi- While there are only expert opinions concerning the burned dence level IVa). area (%TBSA), it is a fundamental index for the evaluation of the severity of burns in the published work on the prognosis CQ3: ARE ARTZ’S CRITERIA USEFUL FOR THE of burns.14–29 Also, as it has been suggested by many to be SEVERITY EVALUATION OF BURNS? useful for the prognosis, the recommendation level was set at B. Many papers have mentioned age (evidence level: IVa– Remarks on recommendation: The use of Artz’s criteria or their V)14–16,18,20,21,24,25 and airway burn (evidence level IVa– modification (Moylan’s criteria) as a tool for the severity evalua- IVb),15,21,23,25,26,29 and some have reported the area of third- tion of burns is recommended as an option. degree burn (evidence level: IVa),24,25 as prognostic factors. Recommendation level: C1. All studies involved hundreds to thousands of burn patients, Comments: so their recommendation levels were set similarly to that of Artz’s criteria and their modification (Moylan’s criteria) are in the burned area. The evidence levels of the burn index26 the widest clinical use for the severity evaluation of burns and and PBI17 are IVa–IVb, but their recommendation level was are practical as a severity scale. However, the evidence level set at B, as they are in wide clinical use in Japan. There is is VI for both, because there are only expert opinions.12,13 also the published work suggesting that burns due to sui- Artz’s criteria and their modification (Moylan’s criteria) grade cide attempts27 and complication by psychiatric disorders24 the severity of burns according to their area, depth and contribute to the mortality rate. complications, and show at which facilities the patients should be treated (Table 2). REFERENCES

14 Tobiasen J, Hiebert JH, Edlich RF. Prediction of burn Table 2. Artz’s criteria mortality. Surg Gynecol Obstet 1982; 154: 711–714. (evidence Critical burns (must be referred to a well-equipped general level IVa). hospital that has a surgeon experienced in burn care) 15 Ryan CM, Schoenfeld DA, Thorpe WP, Sheridan RL, Cassem EH, 2° Burns of over 30% TBSA Tompkins RG. Objective estimates of the probability of death from 338 – 3° Burns of face, hands, feet over 10% TBSA burn injuries. N Engl J Med 1998; : 362 366. (evidence level IVa). Burns complicated by: 16 Iwasaki Y, Okabayashi K, Hatano Y, Mihara S, Noda H, Sera A, Respiratory tract injury Yamamoto S. Treatment of 55 children with severe burns com- Major soft tissue injury pared with 121 adult cases. Jpn J Dermatol 1997; 107: 1253–1261. Fractures (evidence level IVb). Electrical burns 17 Iwasaki Y, Takahashi H, Mori T, Yamamoto S, Miyamoto Y. A Moderate burns (may be treated in a small community hospital) study of the cases of fatal severe burn relationship of burn 2° of 15–30% TBSA index, age, inhalation injury and surgical treatment to the prog- – 3° of less than 10% TBSA, except hands, face, feet nosis. Rinsho Derma (Tokyo) 1991; 33: 1387 1392. (evidence Minor burns (may be treated on an outpatient basis) level IVb). 18 Saffle JR, Gibran N, Jordan M. Defining the ratio of outcomes to 2° of less than 15% TBSA resources for triage of burn patients in mass casualties. J Burn ° 3 of less than 2% TBSA Care Rehabil 2005; 26: 478–482. (evidence level V). 19 Berry CC, Patterson TL, Wachtel TL, Frank HA. Behavioural factors Artz and Moncrief (1969).12 TBSA, total body surface area. in burn mortality and length of stay in hospital. Burns 1984; 10: 409–414. (evidence level IVb). REFERENCES 20 Moreau AR, Westfall PH, Cancio LC, Mason AD Jr. Development and validation of an age-risk score for mortality predication after 12 Artz CP, Moncrief JA. The Treatment of Burns. Philadelphia, PA: thermal injury. J Trauma 2005; 58: 967–972. (level IVa). – W.B. Saunders, 1969; 94 98. (evidence level VI). 21 Belgian Outcome in Burn Injury Study Group. Development and 13 Moylan JA. First aid and transportation of burned patients. In: Artz validation of a model for prediction of mortality in patients with CP, Moncrief JA, Pruitt BA Jr, eds. Burns: A Team Approach. acute burn injury. Br J Surg 2009; 96: 111–117. (evidence level – Philadelphia, PA: W.B. Saunders, 1979; 151 158. (evidence IVb). level VI). 22 George RL, McGwin G Jr, Schwacha MG et al. The association between sex and mortality among burn patients as modified by age. J Burn Care Rehabil 2005; 26: 416–421. (evidence level IVa). CQ4: WHAT ARE USEFUL AS PROGNOSTIC 23 Lionelli GT, Pickus EJ, Beckum OK, Decoursey RL, Korentager RA. FACTORS AND FOR THE PROGNOSIS OF A three decade analysis of factors affecting burn mortality in the BURNS? elderly. Burns 2005; 31: 958–963. (level IVa). 24 Berry CC, Wachtel TL, Frank HA. An analysis of factors which pre- Remarks on recommendation: The presence or absence of air- dict mortality in hospitalized burn patients. Burns 1982; 9:38–45. way damage, area of third-degree burn, burned area (percent- (evidence level IVa). 25 Benito-Ruiz J, Navarro-Monzonis A, Baena-Montilla P, Mirabet- age relative to the TBSA: %TBSA), PBI and burn index are Ippolito V. An analysis of burn mortality: a report from a Spanish recommended as prognostic factors (B). regional burn centre. Burns 1991; 17: 201–204. (evidence level Recommendation level: B. IVa).

guide.medlive.cn The wound/burn guidelines – 6

26 Kobayashi K, Ikeda H, Higuchi R et al. Epidemiological and out- REFERENCES come characteristics of major burns in Tokyo. Burns 2005; 31 (Suppl 1): S3–S11. (evidence level IVa). 30 Artz CP, Moncrief JA. The Treatment of Burns, 2nd edn. Philadel- 27 Thombs BD, Bresnick MG. Mortality risk and length of stay associ- phia, PA: W.B. Saunders, 1969; 94–98. ated with self-inﬂicted burn injury: evidence from a national sample 31 Pham TN, Cancio LC, Gibran NS. American Burn Association Prac- of 30,382 adult patients. Crit Care Med 2008; 36: 118–125. (evi- tice Guidelines Burn Shock Resuscitation. J Burn Care Res 2008; dence level IVa). 29(1): 257–266. 28 Kerby JD, McGwin G Jr, George RL, Cross JA, Chaudry IH, Rue 32 American Burn Association. Advanced Burn Life Support Course LW 3rd. Sex differences in mortality after burn injury: results of Providers Manual. Chicago, IL: American Burn Association, 2001. analysis of the National Burn Repository of the American Burn 33 Atiyeh BS, Gunn SW, Hayek SN. State of the art in burn treatment. Association. J Burn Care Res 2006; 27: 452–456. (evidence level World J Surg 2005; 29: 131–148. (evidence level VI). IVa). 34 Warden GD. Burn shock resuscitation. World J Surg 1992; 16:16– 29 Meshulam-Derazon S, Nachumovsky S, Ad-El D, Sulkes J, Hauben 23. (evidence level VI). DJ. Prediction of morbidity and mortality on admission to a burn 35 Monafo WW. Initial management of burns. N Engl J Med 1996; unit. Plast Reconstr Surg 2006; 118: 116. (evidence level IVa). 335: 1581–1586. (evidence level VI). 36 Hettiaratchy S, Papini R. Initial management of a major burn: II – assessment and resuscitation. BMJ 2004; 329: 101–103. (evidence SYSTEMIC MANAGEMENT: FLUID level VI). RESUSCITATION 37 Moylan JA. First aid and transportation of burned patients. In: Artz CP, Moncrief JA, Pruitt BA Jr, eds. Burns: A Team Approach. CQ5: WHAT KIND OF PATIENTS HAVE – INDICATIONS FOR FLUID RESUSCITATION? Philadelphia, PA: W.B. Saunders, 1979; 151 158. (evidence level VI).

Remarks on recommendation: Fluid resuscitation is recom- CQ6: WHEN SHOULD EARLY FLUID mended to adults with a burned area of 15% TBSA or higher RESUSCITATION BE INITIATED? and children with a burned area of 10% TBSA or higher. How- ever, early fluid resuscitation may be initiated in patients with a Remarks on recommendation: In patients who require fluid smaller burned area depending on the general condition. resuscitation, it is recommended to initiate it as early as possi- Recommendation level: B. ble after injury. Comments: Recommendation level: B. There has been no detailed report on the evaluation of the Comments: appropriateness of fluid resuscitation based on the injured Concerning the time of initiation of early fluid resuscitation, area in adults, and the evidence level is VI as there are only there are case–control studies,38,39 and the evidence level is expert opinions. However, according to Artz’s diagnostic cri- IVb, but the recommendation level was set at B on the basis teria,30 the area of minor burns manageable by outpatient of consensus of the committee. care is a second-degree burn area of 15% or less. When When the burned area is 15–20% or greater, hypovolemic patients with extensive burned area are treated by hospital- shock is caused by an increase in the vascular permeability ization, fluid resuscitation is considered, and is actually imple- without appropriate fluid resuscitation. Edema often occurs mented as, a nearly essential treatment. Therefore, the during the first 6–8 h and persists for 18–24 h or longer.40,41 recommendation level was set at B. In children, also, there Also, in 76 adult burn patients who developed renal insuffi- are only expert opinions, and the evidence level is VI. Accord- ciency, the time until the beginning of early fluid resuscitation ing to the criteria of the American Burn Association, fluid was reported to have differed significantly between those who resuscitation should be initiated when the burned area is 20% survived and those who died (1.7 Æ 1.0 vs 4.4 Æ 21.1 h).38 TBSA or greater.31 Also, as patients with second-degree In a review of 24 patients treated in 1966–1983 and 36 burns affecting 10% or more of the body surface area are patients treated in 1984–1997, the mortality rate was 100% referred to a burn treatment center according to the in the former group but decreased to 56% in the latter. The Advanced Burn Life Support,32 we judged that fluid resuscita- time from injury to the beginning of fluid resuscitation was tion should be performed in children with a burned area of 8.6 Æ 1.7 and 3.0 Æ 0.5 h, respectively. Also, among those 10% TBSA or greater. Moreover, the recommendation level treated after 1984, fluid resuscitation was started earlier in was set at B on the basis of consensus of the committee. those who survived than in those who died (1.7 Æ 0.5 vs According to Artz’s criteria, treatment by hospitalization is 4.8 Æ 0.9 h).41 indicated for patients with a third-degree burn area of 2% or greater, so fluid resuscitation may as well be initiated in the acute period of burns. Also, hypovolemic shock early after REFERENCES

injury has been reported to be avoided by appropriate ﬂuid 38 Chrysopoulo MT, Jeschke MG, Dziewulski P, Barrow RE, Herndon 31,33–36 resuscitation. DN. Acute renal dysfunction in severely burned adults. J Trauma Artz’s criteria and their modiﬁcation (Moylan’s criteria)37 are 1999; 46: 141–144. (evidence level IVb). guidelines for the severity grading of burns according to 39 Jeschke MG, Barrow RE, Wolf SE, Herndon DN. Mortality in burned children with acute renal failure. Arch Surg 1998; 133: 752– their area, depth and complications, and for the selection of 756. (evidence level IVb). facilities appropriate for their treatment (see Table 2 con- 40 Monafo WW. Initial management of burns. N Engl J Med 1996; cerning CQ3). 335: 1581–1586. (evidence level VI).

guide.medlive.cn Y. Yoshino et al.

41 Hettiaratchy S, Papini R. Initial management of a major burn: II – group than in the control group with a relative risk of 2.40 assessment and resuscitation. BMJ 2004; 329: 101–103. (evidence (range, 1.11–5.19) in burn patients, indicating that colloid level VI). administration increased the mortality rate.46 In a report of evaluation in 70 patients with burns of 20% TBSA or less, CQ7: WHAT SHOULD BE USED FOR I.V. FLUID aged 19 years or below, treated by administrating colloid RESUSCITATION? while maintaining the serum albumin level at 2.5–3.5 g/dL (36 patients) or administrating colloid only when the serum Remarks on recommendation: The use of isotonic crystalloid albumin level decreased to less than 1.5 g/dL (34 patients), resuscitation preparations (lactated Ringer’s solution, acetated no difference was observed in complications, the mortality Ringer’s solution) is recommended for fluid resuscitation (B). rate, duration of hospitalization and necessity of manage- The concomitant use of colloid and hypertonic lactated ment using a respirator.47 saline (HLS) are recommended as an option for fluid resuscita- From these observations, colloid administration is consid- tion (C1). ered to reduce the total volume of infusion and suppress the Recommendation level: B and C1. increase in the IAP but not to be effective at present for Comments: improving the life prognosis. However, as a decrease in the Concerning the usefulness of isotonic crystalloid resuscita- colloid osmotic pressure exacerbates edema in non-burned tion preparations for initial fluid resuscitation of burn areas, colloid administration has been recommended by patients, there are only expert opinions, and the evidence some when hypoalbuminemia or a decrease in the colloid level is VI. There are RCT comparing an isotonic crystalloid osmotic pressure 8–12 h after injury is affecting the respira- resuscitation preparation and colloid and reporting no tion or circulation,48 and fluid resuscitation incorporating col- significant difference,42,43 and one meta-analysis comparing loid administration such as the Evens method and Brooke the mortality rate between patients with trauma, burn and method is performed in actual clinical practice. postoperative patients treated by crystalloid and those When 14 patients in the HLS group and 22 patients in the treated by HLS infusion and reporting no significant differ- lactate Ringer’s solution group were compared by maintain- ence.44 Also, as colloid or HLS have not been shown to be ing the urine volume at 0.5–1.0 mL/kg per h, the necessary more advantageous than crystalloid, the recommendation infusion volume was 3.1 Æ 0.9 versus 5.2 Æ 1.2 mL/24 h level was set at B for crystalloid resuscitation, which are per kg 9 %TBSA, respectively, the urine volume could be the most widely used, and C1 for concomitant colloid maintained with a smaller infusion volume, IAP and maxi- administration and HLS on the basis of consensus of the mum inspiratory pressure were significantly lower, and the committee. incidence of intra-abdominal hypertension was lower (14% Infusion of colloids immediately after burn injury, a period vs 50%), in the HLS than lactate Ringer’s solution group.49 with enhanced vascular permeability, has been reported to However, there is also a report that the incidence of renal have no advantage compared with crystalloid resuscita- insufficiency and mortality rate were higher in the HLS than tion.45 In an RCT in which 79 patients with burns were lactated Ringer’s solution group and that no difference was divided into those treated with a lactated Ringer’s solution observed in the total infusion volume.50 According to a and those treated with a colloid (2.5% albumin) plus lactated meta-analysis evaluating whether or not HLS reduces the Ringer’s solution, a larger volume of infusion was necessary mortality rate of hypovolemic patients, when a hypotonic, in the lactated Ringer’s solution group than in the colloid isotonic or nearly isotonic solution was administrated to plus lactated Ringer’s solution group (3.81 vs 2.98 mL/kg trauma, burn and postoperative patients, the relative risk of bodyweight/%TBSA). However, no significant improvement death in the HLS-treated group was 0.84 in trauma, 1.49 in in the circulation was observed even in the colloid plus lac- burn and 0.51 in postoperative patients.44 tated Ringer’s solution group, and pleural effusion increased In conclusion, while no data indicating that HLS has a higher in the period of diuresis.42 Also, when the intravascular pres- survival-improving effect than an isotonic solution have been sure was measured as the intra-abdominal pressure (IAP) in obtained to the present, it is considered to be effective for 15 patients administrated lactated Ringer’s solution (Park- reducing the total infusion volume and suppressing the land method) and 16 administrated a colloid, the IAP increase in the IAP. HLS is prepared by adding sodium to increased significantly in the lactated Ringer’s solution lactated Ringer’s solution. It was devised to supplement group, and more solution was needed for the initial infusion ECF and sodium, which are lost after burn, and to reduce than in the colloid group. In both groups, a correlation was the total infusion volume compared with an isotonic solution. observed between the total volume of infusion and IAP, and, Monafo HLS, Fox HLS and Osaka University HLS are known while the IAP remained less than the complication threshold as its variations. (25 mmHg), and the treatment was effective for controlling the increase in the IAP, in the plasma administration group, 43 no clear difference was noted in survival. REFERENCES In a study evaluating the relationship between the colloid administration and mortality rate in severely injured patients, 42 Goodwin CW, Dorethy J, Lam V, Pruitt BA Jr. Randomized trial of the mortality rate was higher in the colloid administrated efficacy of crystalloid and colloid resuscitation on hemodynamic

guide.medlive.cn The wound/burn guidelines – 6

response and lung water following thermal injury. Ann Surg 1983; the Parkland method or invasive intrathoracic blood volume 197: 520–531. (evidence level II). monitoring, the infusion volume during the first 24 h was sig- 43 O’Mara MS, Slater H, Goldfarb IW, Caushaj PF. A prospective, ran- nificantly greater in the intrathoracic blood volume monitor- domized evaluation of intra-abdominal pressures with crystalloid and colloid resuscitation in burn patients. J Trauma 2005; 58: ing group, and intravascular dehydration was observed 1011–1018. (evidence level II). within 48 h by the Parkland method, but there was no differ- 44 Bunn F, Roberts I, Tasker R, Akpa E. Hypertonic versus near isotonic ence in preload or the cardiac output, or in the mortality rate crystalloid for fluid resuscitation in critically ill patients. Cochrane or incidence of complications.58 Therefore, crystalloid resus- Database Syst Rev, 2004; (3): CD002045. (evidence level I). 45 Monafo WW. Initial management of burns. N Engl J Med 1996; citation in amounts greater than those indicated by the 335: 1581–1586. (evidence level VI). Parkland method is not considered to improve preload or 46 Cochrane Injuries Group Albumin Reviewers. Human albumin admin- the cardiac output. While initial infusion therapy is still per- istration in critically ill patients: systematic review of randomised formed according to the Parkland method at many facilities controlled trials. BMJ 1998; 317: 235–240. (evidence level I). of the world,59,60 further evaluation is awaited for a conclu- 47 Greenhalgh DG, Housinger TA, Kagan RJ et al. Maintenance of serum albumin levels in pediatric burn patients: a prospective, ran- sion concerning the appropriate volume and rate of fluid domized trial. J Trauma 1995; 39:67–74. (evidence level II). resuscitation. 48 Warden GD. Burn shock resuscitation. World J Surg 1992; 16:16– 23. (level VI). 49 Oda J, Ueyama M, Yamashita K et al. Hypertonic lactated saline REFERENCES resuscitation reduces the risk of abdominal compartment syndrome in severely burned patients. J Trauma 2006; 60:64–71. 51 Kramer G, Hoskins S, Copper N, Chen JY, Hazel M, Mitchell C. (level III). Emerging advances in burn resuscitation. J Trauma 2007; 62: S71– 50 Huang PP, Stucky FS, Dimick AR, Treat RC, Bessey PQ, Rue LW. S72. (evidence level I). Hypertonic sodium resuscitation is associated with renal failure 52 Baxter CR, Shires GT. Physiological response to crystalloid resus- and death. Ann Surg 1995; 221: 543–554. (level IVb). citation of severe burns. Ann NY Acad Sci 1968; 150: 874–894. 53 Baxter CR. Problems and complications of burn shock resuscitation. Surg Clin North Am 1978; 58: 1313–1322. CQ8: HOW SHOULD THE INITIAL INFUSION 54 Friedrich JB, Sullivan SR, Engrav LH et al. Is supra-Baxter resusci- VOLUME BE CALCULATED? tation in burn patients a new phenomenon? Burns 2004; 30: 464– 466. Remarks on recommendation: It is recommended to initiate 55 Mitra B, Fitzgerald M, Cameron P, Cleland H. Fluid resuscitation in – fluid resuscitation using the Parkland method (also called the major burns. Anz J Surg 2006; 76:35 38. 56 Dulhunty JM, Boots RJ, Rudd MJ, Muller MJ, Lipman J. Increased Baxter method). fluid resuscitation can lead to adverse outcomes in major-burn Recommendation level: B. injured patients, but low mortality is achievable. Burns 2008; 34: Comments: 1090–1097. There is one meta-analysis concerning the initial fluid resus- 57 Klein MB, Hayden D, Elson C et al. The association between fluid administration and outcome following major burn: a multicenter citation,51 and the evidence level is I. While the Parkland study. Ann Surg 2007; 245: 622–628. method is widely used, the necessary infusion volume has 58 Holm C, Mayr M, Tegeler J. A clinical randomized study on the been reported to have exceeded that calculated by this effects of invasive monitoring on burn shock resuscitation. Burns method, so its recommendation level was reduced to B. 2004; 30: 798–807. Baxter carried out an animal experiment for the hemody- 59 Nguyen TT, Gilpin DA, Meyer NA, Herndon DN. Current treatment of severely burned patients. Ann Surg 1996; 223:14–25. namic evaluation using a radioisotope in the acute period of 60 Hettiaratchy S, Papini R. Initial management of a major burn: II – burn injury and showed that infusion at 3.7–4.3 mL/kg per assessment and resuscitation. BMJ 2004; 329: 101–103. %TBSA was necessary, that functional extracellular fluid (ECF) decreased rapidly after burn injury depending on the CQ9: WHAT SHOULD BE USED AS THE INDEX burned area, but that shock due to burn could be avoided, FOR THE DETERMINATION OF THE INFUSION and the mortality rate could be reduced, by the administra- RATE? tion of lactated Ringer’s solution.52 There is also a report that, when lactated Ringer’s solution was administrated to Remarks on recommendation: The urine volume is recom- patients with a target urine volume of 40 mL/h and accord- mended as an index for the infusion rate. The infusion rate ing to the level of consciousness, the infusion volume during should be adjusted to maintain the urine volume at 0.5 mL/kg the 24 h after injury was 3.7–4.3 mL/kg per %TBSA in 70% per h or 30–50 mL/h or more in adults, and 1–2 mL/kg per h or of adults and 98% of children aged 12 years or less.53 more in children. Recently, the initial infusion volume greater than that calcu- Recommendation level: B. lated by the Parkland method has been reported to have Comments: been necessary,51,54,55 but excessive infusion has been sug- There are only expert opinions about indices of the appro- gested to promote edema and increase compartment syn- priate volume and rate of initial infusion, and the evidence drome of the limbs, pneumonia, acute respiratory distress level is VI. However, the recommendation level was set at B, syndrome, multiple organ failure, sepsis and the mortality because the urine volume per hour reflects the organ blood rate.56,57 According to a study in which 50 burn patients flow and is widely accepted as an index for hemodynamic with a burned area of 20% TBSA or higher were treated by evaluation.

guide.medlive.cn Y. Yoshino et al.

The objective of initial fluid resuscitation is to resolve hypov- Recommendation level: B. olemic shock, and the urine volume, which reflects the renal Comments: blood flow, is widely used as an index for the evaluation of Concerning the diagnosis of inhalation injury using the broncho- – the organ blood fow.61 63 However, caution is needed as scope, there is a cohort study,66 and the evidence level is IVa. the urine volume cannot be used as the sole index in However, the recommendation level was set at B, because it is patients with compromised renal function. The hemodynam- a widely practiced examination with a high diagnostic value. ics should also be evaluated using other general vital signs Presence of soot inside the bronchi and pallor and ulcera- (e.g. blood pressure, heart rate, peripheral circulation and tion of the bronchial mucosa observed by bronchoscopy tachypnea), central venous pressure and lactate level. have been reported to be in agreement with diagnoses of inhalation injury.67,68

REFERENCES REFERENCES 61 Warden GD. Burn shock resuscitation. World J Surg 1992; 16:16– 23. (evidence level VI). 66 Masanes MJ, Legendre C, Lioret N, Saizy R, Lebeau B. Using 62 Monafo WW. Initial management of burns. N Engl J Med 1996; bronchoscopy and biopsy to diagnose early inhalation injury: – 335: 1581 1586. (evidence level VI). macroscopic and histologic findings. Chest 1995; 107: 1365–1369. – 63 Hettiaratchy S, Papini R. Initial management of a major burn: II (evidence level IVa). – assessment and resuscitation. BMJ 2004; 329: 101 103. (evidence 67 American Burn Association. Inhalation injury: diagnosis. J Am Coll level VI). Surg 2003; 196: 307. 68 Masanes MJ, Legendre C, Lioret N, Maillard D, Saizy R, Lebeau B. Fiberoptic bronchoscopy for the early diagnosis of subglottal SYSTEMIC MANAGEMENT: AIRWAY BURNS inhalation injury: comparative value in the assessment of progno- CQ10: WHAT ARE FACTORS THAT SUGGEST sis. J Trauma 1994; 36:59–67. AIRWAY INJURY? Remarks on recommendation: Circumstances of injury (injury in CQ12: IS PLAIN CHEST RADIOGRAPHY a narrow space due to inhalation of hot vapor or liquid) and USEFUL FOR THE DIAGNOSIS OF physical findings (soot in the mouth or sputum, burned ends of RESPIRATORY DISORDERS DUE TO nasal hair, burns of the face) are recommended as findings that INHALATION INJURY? suggest airway burns. Remarks on recommendation: It is recommended to serially Recommendation level: B. perform plain chest radiography in the acute period for the Comments: early diagnosis of respiratory disorders. There is a case–control study investigating the presence or Recommendation level: B. absence of airway burns according to physical findings,64 Comments: and the evidence level is IVb. However, the recommendation Concerning the diagnosis of respiratory disorders by plain level was set at B, because they are common diagnostic chest radiography, there are cohort studies,69,70 and the evi- indices and can be examined easily. dence level is IVa. However, the recommendation level was Most experts use the circumstances of injury and physical set at B, because it is a useful examination that can be per- findings as non-invasive indices of inhalation injury.65 In formed relatively easily. patients requiring intubation, airway burns are reported to The grading by plain chest radiography correlated well with be positively correlated with soot in the oral cavity the extravascular lung water content, intrapulmonary shunt (P < 0.001), burns of the face (P = 0.025) and burns of the ratio (Qs/Qt) and static lung compliance.69 Abnormalities trunk (P = 0.025), and the correlations to be higher than that detected by early plain chest radiography are important with edema of the vocal cord detected by laryngoscopy.64 prognostic factors that make the selection of patients that are likely to need respirator management possible.70 It is an easy-to-perform examination compared with computed REFERENCES tomography, and serial radiographic evaluation is recom-

64 Madnani DD, Steele NP, de Vries E. Factors that predict the need mended in the acute period. for intubation in patients with smoke inhalation injury. Ear Nose Throat J 2006; 85: 278–280. (evidence level IVb). 65 American Burn Association. Inhalation injury: diagnosis. J Am Coll REFERENCES Surg 2003; 196: 307. (evidence level VI). 69 Peitzman AB, Shires GT 3rd, Teixidor HS et al. Smoke inhalation injury: evaluation of radiographic manifestations and pul- CQ11: IS BRONCHOSCOPY USEFUL FOR THE monary dysfunction. J Trauma 1989; 29: 1232–1239. (evidence DIAGNOSIS OF AIRWAY INJURY? level IVa). 70 Lee MJ, O’Connell DJ. The plain chest radiograph after Remarks on recommendation: The diagnosis by bronchoscopy acute smoke inhalation. Clin Radiol 1988; 39:33–37. (evidence is recommended. level IVa).

guide.medlive.cn The wound/burn guidelines – 6

CQ13: SHOULD ENDOTRACHEAL INTUBATION is also a report that laryngeal edema was alleviated, and BE PERFORMED WHEN INHALATION INJURY the reintubation rate was reduced, in non-burn adult IS SUSPECTED? patients who underwent intubation for 36 h or longer with systemic steroid administration before extubation,76 sug- Remarks on recommendation: When inhalation injury is sus- gesting that the treatment is useful for alleviating edema. pected, preventive intubation is recommended if possible. However, these patients cannot be compared with those Recommendation level: B. with damages in the airway mucosa due to differences in Comments: the condition. There is a cohort study about preventive endotracheal intubation,71 and the evidence level is IVa. However, the recommendation level was set at B because of the seriousness of REFERENCES the disadvantage when intubation becomes impossible later. Respiratory disorders associated with burns may be caused 73 Levine BA, Petroff PA, Slade CL, Pruitt BA Jr. Prospective trials of by restriction of respiratory motions and compression of the dexamethasone and aerosolized gentamicin in the treatment of inhalation injury in the burned patient. J Trauma 1978; 18: 188– trachea due to burns of the neck/chest as well as airway 193. (evidence level II). 72 injury. Therefore, whether the patient should be intubated 74 Robinson NB, Hudson LD, Riem M et al. Steroid therapy following or not cannot be determined according to the presence or isolated smoke inhalation injury. J Trauma 1982; 22: 876–879. absence of airway injury alone. However, if airway edema is 75 Cha SI, Kim CH, Lee JH et al. Isolated smoke inhalation injuries: acute respiratory dysfunction, clinical outcomes, and short-term caused by burns of the face/neck or airway, preventive intu- evolution of pulmonary functions with the effects of steroids. Burns bation is recommended, because intubation may become 2007; 33: 200–208. difficult with the progression of the course. Also, there is a 76 Francßois B, Bellissant E, Gissot V et al. 12-h pretreatment with report that early preventive intubation and respiratory man- methylprednisolone versus placebo for prevention of postextuba- agement by continuous positive airway pressure may have tion laryngeal oedema: a randomised double-blind trial. Lancet 2007; 369: 1083–1089. contributed to the prevention of respiratory organ-related deaths early after burns.71 INFECTION CONTROL CQ15: IS PREVENTIVE SYSTEMIC REFERENCES ADMINISTRATION OF ANTIBIOTICS EARLY AFTER BURNS USEFUL? 71 Venus B, Matsuda T, Copiozo JB, Mathru M. Prophylactic intubation and continuous positive airway pressure in the management of Remarks on recommendation: In patients with contaminated – inhalation injury in burn victims. Crit Care Med 1981; 9: 519 523. wounds, immunocompromised patients such as those with (evidence level IVa). diabetes, children and perioperative patients, it is recom- 72 Gartner R, Griffe O, Captier G, Selloumi D, Otman S, Brabet M, Baro B. Acute respiratory insufficiency in burn patients from smoke mended to determine target microorganisms in consideration inhalation. Pathol Biol 2002; 50: 118–126. of facility and local characteristics as well as the results of bacterial cultures from the wound and to perform preventive CQ14: IS STEROID ADMINISTRATION USEFUL systemic administration of antibiotics as an option (C1). FOR THE MANAGEMENT OF INHALATION Uniform preventive systemic administration of antibiotics INJURY? cannot be recommended (at present) because of the absence of sufficient evidence supporting its effectiveness (C2). Remarks on recommendation: Steroid administration (systemic Recommendation level: C1 for administration according to or topical) for the treatment of inhalation injury cannot be recom- the patient’s condition and situation. C2 for uniform preventive mended (at present) because of the lack of sufficient evidence. systemic administration. Recommendation level: C2. Comments: Comments: Concerning preventive systemic administration in the periop- Concerning the systemic steroid administration for inhalation erative period, there are two RCT, and the evidence level is injury, there is an RCT,73 and the evidence level is II. How- II.77,78 While it may improve the survival rate of skin grafts or ever, systemic steroid administration has not been shown to reduce the incidence of bacteremia, the recommendation be useful for reducing the mortality rate or preventing com- level was set at C1 due to the lack of data that it improved plications. The recommendation level was set at C2 also in the survival rate. consideration of increased susceptibility to infection in a There is an RCT concerning uniform systemic administration state of disruption of the mucosal barrier function due to of antibiotics for the prevention of infection of burns, and burns. The recommendation level of topical steroid adminis- the evidence level is II.79 In this trial, no improvement in the tration was set similarly. outcome or decrease in the incidence of infection was There are reports that systemic steroid administration observed despite uniform systemic administration of antibi- caused no difference in lung-related conditions or the otics. Moreover, as the treatment may induce microbial sub- mortality rate in burn patients with airway injury.74,75 There stitution, the recommendation level was set at C2.

guide.medlive.cn Y. Yoshino et al.

There are many negative reports concerning uniform preven- complications such as diabetes and are immunocompro- tive systemic administration of antibiotics. Ergun} et al. trea- mised, and to prophylactically administrate antibiotics to ted 77 children with extensive burns with and without which the bacteria are susceptible.85 Rashid et al. adminis- preventive systemic administration of antibiotics in 47 and trated antibiotics for the prevention of TSS in children with 30, respectively, and reported that the frequency of wound burns and reported a decrease in its incidence.86 In the peri- infection was significantly higher in the treatment (21.3%) operative period, also, as Staphylococcus aureus and Pseu- than non-treatment (16.7%) group, that seven of the eight domonas aeruginosa are predominantly and widely patients who developed sepsis belonged to the treatment detected, Wolf et al. stated that they administrate van- group, that the duration of hospitalization was longer in the comycin and amikacin in combination between 1 h before treatment group and that the treatment was related to sec- and 24 h after surgery.87 ondary infections of other sites (respiratory organs, urinary Regarding the effects on the survival of skin grafts, Ramos tract).79 In a multicenter collaborative study carried out in et al. compared the survival rate of 90 skin grafts in 77 Italy, 634 patients with extensive burns (mean age, patients (mean age, 41.7 years; mean burned area, 21.8% ~40 years; mean burned area, 35% TBSA) were treated by TBSA) between 44 and 46 surgeries performed with and topical application of silver sulfadiazine and 4-day adminis- without topical application of polymyxin and preventive sys- tration of pefloxacin (a quinolone). As a result, 104 (16%) temic administration of antibiotics and reported that any part showed no infection, but the burns of all these patients were of the skin graft was lost in 23% and 50%, and 10% or relatively minor, and bacteria resistant to quinolones and greater area of the skin graft was lost in 9% and 35%, aminoglycosides increased after the administration, so the respectively, with significant differences.79 usefulness of preventive systemic administration of antibi- Because of the marked variation in underlying disease, and otics by this protocol could not be confirmed.80 condition of the wound, among the patients, opinions as to Concerning studies on minor burns, Boss et al. retrospec- what kind of patients are candidates for preventive adminis- tively compared the wound infection rate between 133 who tration of antibiotics and which antibiotics should be used underwent systemic administration of antibiotics and 161 vary widely. In patients with contaminated wounds, immuno- who did not of the 294 outpatients with burns and reported compromised patients such as those with diabetes, children that there was no difference in the infection rate (3.8% vs and perioperative patients, preventive administration of 3.1%) and that, while antibiotics were administrated to a antibiotics effective for the control of bacteria isolated by significantly higher percentage of patients in those with a bacterial cultures or those suspected to be infecting the burned area of 5% TBSA or more than in those with a patient should be considered. burned area of less than 5% TBSA, the infection rate was If severe infection or sepsis has occurred in burn patients, it not reduced in the first group.81 should be treated according to the international guidelines Various reports and opinions have been presented concern- for management of severe sepsis and septic shock: 2008.88 ing what kind of patients should receive preventive adminis- Supplementary comments: According to the systematic tration of antibiotics. In children, the incidence of toxic review concerning the preventive systemic administration of shock syndrome (TSS) is reported to be higher than in antibiotics and outcome in severely burned patients issued in adults and to be often lethal.82 Sheridan et al. compared February 2010,89 the mortality rate was significantly lower with children with burns administrated antibiotics for the preven- than without the treatment. The review states, “The current tion of group A b-hemolytic streptococcal infection and guidelines do not recommend preventive systemic administra- those administrated antibiotics only when group A b-hemo- tion of antibiotics except in the perioperative period, but the lytic streptococci were detected by cultures of samples from results of this review are contradictory to this view. Also, as the wound and considered the treatment unnecessary, the data collected include those based on weak methodolo- because the incidence of group A b-hemolytic streptococcal gies, a large-scale randomized controlled trial is necessary for infection was originally low, and because no difference was the future.” observed in its incidence with or without preventive administration.83 Patients with extensive burns have been reported to temporarily develop bacteremia in wound lavage and sur- REFERENCES gery.84 However, according to Steer et al., who evaluated 77 Ergun€ O, Celik A, Ergun€ G, Ozok G. Prophylactic antibiotic use in the incidence of bacteremia and outcome after perioperative pediatric burn units. Eur J Pediatr Surg 2004; 14:422–426. (evi- preventive administration of teicoplanin, the incidence of dence level II). bacteremia was reduced, but the outcome was comparable 78 Steer JA, Papini RP, Wilson AP, McGrouther DA, Nakhla LS, between the teicoplanin-treated and non-treated groups.78 Parkhouse N. Randomized placebo-controlled trial of On the other hand, there are considerable numbers of teicoplanin in the antibiotic prophylaxis of infection following manipulation of burn wounds. Br J Surg 1997; 84: 848–853. (evi- reports suggesting the effectiveness of preventive adminis- dence level II). tration and opinions recommending it in patients considered 79 Ramos G, Resta M, Machare Delgado E, Durlach R, Fernandez to be at high risk of infection and perioperative patients. Canigia L, Benaim F. Systemic perioperative antibiotic prophylaxis Takuma recommended to specify bacteria that may infect may improve skin autograft survival in patients with acute burns. J Burn Care Res, 2008; 29: 917–923. (evidence level II). patients with contaminated wounds, those who have

guide.medlive.cn The wound/burn guidelines – 6

80 Donati L, Periti P, Andreassi A et al. Increased burn patient survival “at burn centers, to usually administer human tetanus with once-a-day high dose teicoplanin and netilmicin. An Italian immunoglobulin (TIG) at 250–500 U and to administer teta- multicenter study. J Chemother 1998; 10:47–57. (evidence level nus toxoid (Tt) to patients who have not acquired complete IVa). 81 Boss WK, Brand DA, Acampora D, Barese S, Frazier WH. Effec- primary immunity or those more than 10 years after the last tiveness of prophylactic antibiotics in the outpatient treatment of vaccination”.90 Concerning wounds in general including burns. J Trauma 1985; 25: 224–227. (evidence level IVa). burns, the American Academy of Pediatrics Advisory Com- 82 Church D, Elsayed S, Reid O, Winston B, Lindsay R. Burn wound mittee on Immunization Practices and Advisory Committee infections. Clin Microbiol Rev 2006; 19: 403–434. 83 Sheridan RL, Weber JM, Pasternack MS, Tompkins RG, Antibiotic on Immunization Practices recommend the administration of Prophylaxis for Group. A streptococcal burn wound infection is not Tt or TIG depending on the patient’s history of inoculation of necessary. J Trauma 2001; 51: 352–355. (evidence level IVa). Tt and condition of the wound (whether or not it is a teta- 84 Mozingo DW, McManus AT, Kim SH, Pruitt BA Jr. Incidence of nus-prone wound).91,98,99 bacteremia after burn wound manipulation in the early postburn Clinically, it is difficult to strictly distinguish between “te- period. J Trauma 1997; 42: 1006–1011. 85 Takuma K. The characteristics of burn wound infection and its con- tanus-prone” and “non-tetanus-prone” wounds, and tetanus trol. MB Derma 2008; 146:54–65. (In Japanese) (evidence level VI). occurs not infrequently from a minor wound such as a 86 Rashid A, Brown AP, Khan K. On the use of prophylactic antibi- scratch sustained during gardening and a burn of 1% – otics in prevention of toxic shock syndrome. Burns 2005; 31: 981 TBSA or less or even without a clear wound. Therefore, 985. (evidence level IVa). 87 Wolf SE, Pruitt BA. Infection in burns. In: Burke AC, ed. Infectious Rhee et al. recommended to “administer Tt and TIG to Diseases in Critical Care Medicine. New York, NY: Informa Health- those more than 10 years after the last vaccination and care, 2007; 507–526. (evidence level VI). those with an unclear state of immunity regardless of the 88 Dellinger RP, Levy MM, Carlet JM et al. Surviving Sepsis Cam- severity of the wound”,92 but, in the present medical cir- paign: international guidelines for management of severe sepsis cumstances in Japan, it is considered difficult to adminis- and septic shock. Crit Care Med 2008; 36: 296–327. (evidence level I). trate Tt or TIG to all patients with traumas including minor 89 Avni T, Levcovich A, Ad-El DD, Leibovici L, Paul M. Prophylactic ones. Also, according to the survey of five emergency med- antibiotics for burns patients: systematic review and meta-analysis. ical facilities in the USA, none of the 504 patients with “te- BMJ 2010; 340: c241. (evidence level I). tanus-prone wounds” in a state of incomplete primary immunity was administrated both Tt and TIG, suggesting a TETANUS gap between the guidelines and actual use of TIG.92 How- CQ16: IS ANTI-TETANUS TREATMENT OF ever, as tetanus can be lethal once it occurs, the adminis- BURNS NECESSARY FOR THE PREVENTION tration of Tt or TIG is recommended for patients with OF TETANUS? incomplete or unclear primary immunity against tetanus and those with contaminated burns more than 5 or 10 years Remarks on recommendation: For contaminated burns, the after the last vaccination depending on the degree of con- administration of tetanus toxoid (Tt) or human tetanus tamination of the wound similar to anti-tetanus treatment immunoglobulin (TIG) is recommended. for wounds in general. In Japan, Takeuchi et al.100 per- Recommendation level: B. formed anti-tetanus preventive treatment in 89 trauma Comments: patients (TIG in 60, Tt in nine, both in 20) and reported no There have been three descriptive studies reviewing the pre- occurrence of tetanus or adverse reactions, but, according vious published work on anti-tetanus treatment for wounds to our review, there is no evaluation or report concerning 90–92 in general including burns, and the evidence level is V. burns. It is recommended to treat contaminated burns similarly to other wounds in general.90 While there is no clear standard for anti-tetanus treatment for burn patients in Japan, the REFERENCES recommendation level was set at B on the basis of consensus of the committee, because tetanus can be lethal once it 90 Church D, Elsayed S, Reid O, Winston B, Lindsay R. Burn – occurs, and because there is an opinion recommending wound infections. Clin Microbiol Rev 2006; 19: 403 434. (evidence 93 level V). anti-tetanus treatment for contaminated burns. 91 Brook I. Current concepts in the management of Clostridium tetani Clostridium tetani is an anaerobic bacterium widely disinfection. Expert Rev Anti Infect Ther 2008; 6: 327–336. (evidence tributed in nature including rice paddies, vegetable fields level V). and house gardens,94 and tetanus may occur following 92 Rhee P, Nunley MK, Demetriades D, Velmahos G, Doucet JJ. Teta- nus and trauma: a review and recommendations. J Trauma 2005; burns.95,96 There is a report that an 18-month-old girl who 58: 1082–1088. (level V). had undergone anti-tetanus vaccination three times and was 93 Aikawa N, Aoki K, Yamazaki M. Burn would infection. Antibiot Che- considered to have complete immunity against tetanus mother 1999; 15: 671–673. (In Japanese) (evidence level VI). developed the disease 11 days after sustaining a burn of 94 Ebisawa I, Takayanagi M, Kurata M, Kigawa M. Density and distri- 25% TBSA.97 For the prevention of tetanus at the time of bution of C. tetani in the ground. J Jpn Assoc Infect Dis 1984; 60: 277–282. (In Japanese). injury including burns, topical treatment of wounds including 95 Miyazawa N, Matsuura Y, Seino H. Severe tetanus with diabetic the removal of foreign bodies and debridement is consid- foot ulcers. J Jpn Soc Intern Med 2005; 94: 1155–1157. (In Japa- ered essential. In addition to it, Church et al. recommended, nese) (evidence level V).

guide.medlive.cn Y. Yoshino et al.

96 Sakaguchi E, Sakai K. Treatment of tetanus in a patient of immersed hydrotherapy may increase the number of bacte- advanced age. Nishinihon J Dermatol 1990; 52: 696–700. (In Japa- ria on the normal skin and other non-infected wounds or nese) (evidence level V). cause infection of wounds and loss of skin grafts. 97 Karyoute SM, Badran IZ. Tetanus following a burn injury. Burns Incl Therm Inj 1988; 14: 241–243. (evidence level V). The above bacteria settle at parts of the hydrotherapy 98 Kruszon-Moran DM, McQuillan GM, Chu SY. Tetanus and diphthe- equipment difficult to sterilize such as stainless plates and ria immunity among females in the United States: are recommen- pipes,105,108 and complete prevention of their settlement is – dations being followed?. Am J Obstet Gynecol 2004; 190: 1070 difficult. However, Akin et al. applied a shower to patients 1076. (evidence level IVb). 99 Larkin JM, Moylan JA. Tetanus following a minor burn. J Trauma on a stretcher covered with a sterilized disposable plastic 1975; 15: 546–548. (evidence level V). sheet and reported that the measure was effective for the 100 Takeuchi Y, Sono M, Iguchi M, Kusafuka H. Management and pre- prevention of infection, with no contamination of wound vention of tetanus in trauma patients. J Jpn Assoc Surg Trauma from the stretcher being observed.109 Patients with exten- 2007; 21: 367–374. (In Japanese) (evidence level V). sive burns are obliged to be hospitalized for a long time and are exposed to physical and psychological stress associated CQ17: IS HYDROTHERAPY (SHOWER, with treatments, surgery and so forth. Although hydrother- BATHING, LAVAGE) USEFUL FOR THE apy is expected to relieve the patient’s psychological stress TREATMENT OF BURNS? and refresh them, there is no published work to our knowl- edge concerning the effects of hydrotherapy on the patient’s Remarks on recommendation: Hydrotherapy is recommended psychology. for patients with minor burns not requiring hospitalization (B). On the other hand, hydrotherapy is recommended by a Because hydrotherapy using shared equipment may induce number of reports for minor burns not requiring hospitaliza- nosocomial infection including P. aeruginosa and methicillin- tion,101,102 and guidance about how to take a shower or resistant S. aureus (MRSA) infections and exacerbate the sur- bath at home is considered to be given on various opportu- vival rate in patients with extensive severe burns, it is recom- nities in daily clinical practice. While we have encountered mended as an option to perform hydrotherapy with anti- no report of comparison of the infection rate between infection measures in patients with a stable general condition hydrotherapy and no hydrotherapy groups, hydrotherapy is and those who are expected to benefit from hydrotherapy (C1). considered recommendable for minor burns in consideration Recommendation level: B for hydrotherapy of relatively of the rich clinical experience in the past. There are reports minor burns not requiring hospitalization. C1 for hydrotherapy that no difference was observed in the infection rate of sim- of extensive severe burns with anti-infection measures. ple wounds that can be closed by primary suturing whether Comments: they were washed with tap water or sterile saline.110,111 The published work on hydrotherapy for patients with rela- Also, according to many expert opinions, minor burns tively minor burns not requiring hospitalization is mostly “should be washed with sterile saline or sterilized expert opinions, and the evidence level is VI.101–104 How- water”,101,103,104 but, when minor burns are regarded as ever, as there are many opportunities for giving guidance simple wounds, the infection rate is not considered to differ concerning taking a shower or bath at home in daily clinical whether they are washed with tap water or sterile saline. practice, the recommendation level was set at B on the Presently, however, there is no report comparing the proce- basis of consensus of the committee in consideration of the dures. huge number of cases accumulated to the present. Con- cerning hydrotherapy for extensive severe burns and their – infection, there is one case control study, and the evidence REFERENCES level is IVb.105 Hydrotherapy for burns is performed at many facilities. 101 Takayanagi K, Kumagai N. Minor burn treatment in an out-patient According to an investigation by a burn unit of the USA and clinic. Jpn J Acute Med 2003; 27:83–84. (In Japanese) (evidence Canada reported in 1994, of the surveyed facilities, level VI). 102 Deguchi E. Management of burns, chemical burns, and electric hydrotherapy was carried out at 94.8%, with immersion per- injuries in children. Jpn J Pediatr Surg 2003; 35: 966–970. (In Japa- formed at 81.4%, and hydrotherapy was performed regard- nese) (evidence level VI). less of the burned area at 82.8% and throughout the period 103 Kawakami M. Emergency management of burn injuries. Jpn J – of hospitalization at 86.9%.106 However, hydrotherapy using Acute Med 2001; 25: 346 348. (In Japanese) (evidence level VI). 104 Suzuki T. Acute burn. J Clin Surg 2004; 59: 343–345. (In Japanese) shared equipment has been suggested to cause nosocomial (evidence level VI). infections including P. aeruginosa and MRSA infec- 105 Simor AE, Lee M, Vearncombe M et al. An outbreak due to mul- tions.105,107,108 In the study by Tredget et al., the mortality tiresistant Acinetobacter baumannii in a burn unit: risk factors for rate, sepsis-related mortality rate, and P. aeruginosa-related acquisition and management. Infect Control Hosp Epidemiol 2002; 23: 261–267. (evidence level IVb). mortality rate were all significantly lower, and the resistance 106 Shankowsky HA, Callioux LS, Tredget EE. North American survey of P. aeruginosa to aminoglycosides was reduced, in a of hydrotherapy in modern burn care. J Burn Care Rehabil 1994; group that received bedside lavage using sterilized water 15: 143–146. and chlorhexidine without immersion compared with a group 107 Embil JM, McLeod JA, Al-Barrak AM et al. An outbreak of methi- immersed using shared equipment.108 They observed that cillin resistant Staphylococcus aureus on a burn unit: potential role

guide.medlive.cn The wound/burn guidelines – 6

of contaminated hydrotherapy equipment. Burns 2001; 27: 681– REFERENCES 688. (evidence level V). 108 Tredget EE, Shankowsky HA, Joffe AM et al. Epidemiology of infec- 112 Snelling CF, Inman RJ, Germann E et al. Comparison of silver sul- tions with Pseudomonas aeruginosa in burn patients: the role of fadiazine 1% with chlorhexidine digluconate 0.2% to silver sulfadi- hydrotherapy. Clin Infect Dis 1992; 15: 941–949. (evidence level V). azine 1% alone in the prophylactic topical antibacterial treatment 109 Akin S, Ozcan M. Using a plastic sheet to prevent the risk of con- of burns. J Burn Care Rehabil 1991; 12:13–18. (evidence level II). tamination of the burn wound during the shower. Burns 2003; 29: 113 Takayanagi K, Kumagai N. Minor burn treatment in an out-patient 280–283. (evidence level V). clinic. Jpn J Acute Med 2003; 27:83–84. (In Japanese) (evidence 110 Valente JH, Forti RJ, Freundlich LF, Zandieh SO, Crain EF. Wound level VI). irrigation in children: saline solution or tap water? Ann Emerg Med 114 Kawakami M. Emergency management of burn injuries. Jpn J 2003; 41: 609–616. Acute Med 2001; 25: 346–348. (In Japanese) (evidence level VI). 111 Moscati RM, Mayrose J, Reardon RF, Janicke DM, Jehle DV. A 115 Suzuki T. Acute burn. J Clin Surg 2004; 59: 343–345. (In Japanese) multicenter comparison of tap water versus sterile saline for wound (evidence level VI). irrigation. Acad Emerg Med 2007; 14: 404–409. 116 Aikawa N, Aoki K, Yamazaki M. Burn would infection. Antibiot Che- mother 1999; 15: 671–673. (In Japanese) (evidence level VI). 117 Natsui M. The principles of wound healing. J Clin Surg 2008; 63: DISINFECTION 915–919. (In Japanese) (evidence level VI). CQ18: IS DISINFECTION USEFUL FOR THE 118 Mizuhara A. Basic management of would. Surgery 2008; 70: 293– PREVENTION OF INFECTION OF BURNS? 300. (In Japanese) (evidence level VI). 119 Available from URL: http://www.health.nsw.gov.au/resources/ Remarks on recommendation: It is recommended as an option gmct/burninjury/pdf/clinical_practice_guidelines.pdf (evidence level VI). to disinfect burns by evaluating the condition of the wound 120 Ward RS, Saffle JR. Topical agents in burn and wound care. Phys along with the causative bacteria and antibacterial spectra of Ther 1995; 5: 526–538. various drugs. 121 Vehmeyer-Heeman M, Van den Kerckhove E, Gorissen K, Boeckx Recommendation level: C1. W. Povidone-iodine ointment: no effect of split skin graft healing – Comments: time. Burns 2005; 31: 489 494. (evidence level IVa). 122 Aiba M, Ninomiya J, Furuya K et al. Induction of a critical elevation Regarding the effectiveness of disinfectants for burns, there of povidone-iodine absorption in the treatment of a burn patient: is one RCT comparing silver sulfadiazine alone and silver report of a case. Surg Today 1999; 29: 157–159. (evidence level V). sulfadiazine plus chlorhexidine,112 and the evidence level is II. The frequency of colonization of S. aureus at the wound DEFECATION CONTROL INSTRUMENTS/ has been shown to be reduced, but the recommendation SYSTEMS level was set at C1, because whether or not the treatment CQ19: IS THE FECAL DIVERSION TUBE improves the outcome is unclear. USEFUL FOR THE PREVENTION OF There are various opinions and reports concerning disinfec- INFECTION OF BURNS AROUND THE ANUS? tion of burns, and the matter still remains controversial. In Japan, some investigators consider that chlorhexidine or Remarks on recommendation: In patients with perianal burns, – povidone iodine should be used for disinfection of burns,113 the use of the fecal diversion tube is recommended as an 116 but others consider that disinfection itself should be option in consideration of the patient’s general condition, and avoided.117,118 The guidelines concerning burn of New state of the wound because it may reduce the frequency of South Wales, Australia,119 recommend that burns “should gauze changes due to contamination by stools and the inci- be washed with 0.05% chlorhexidine gluconate, sponge sat- dence of wound or urinary tract infection. urated with chlorhexidine gluconate, or sterile saline”. Snel- Recommendation level: C1. ling et al. studied 253 burn patients with a mean burned Comments: area of approximately 20% TBSA and reported that the fre- There is one non-randomized comparative trial concerning quency of colonization of S. aureus was reduced by wash- the use of the fecal diversion tube for burn patients,123 and ing the wounds with a mixture of silver sulfadiazine and the evidence level is III. 0.2% chlorhexidine gluconate or soap containing 4% In patients with burns of the gluteal, femoral and perineal chlorhexidine gluconate at gauze changes compared with regions, contamination of the wound associated with defe- topical application of 1% silver sulfadiazine alone.112 cation often poses problems, and the patients are exposed As for povidone iodine, there is a report that it is toxic to to the risk of infection and loss of skin grafts. Also, sedated fibroblasts and epidermal keratinized cells in vitro at clini- patients have fecal incontinence and require gauze change cally used concentrations,120 but there is another report at each bowel movement, and patients with fecal inconti- that no significant difference was observed in the time nence are reported to increase the risk of nosocomial infec- until cure when split-thickness mesh skin grafts were tion including Clostridium difficile infection.124 treated by topical application of povidone iodine or Recently, the fecal diversion tube has been reported to be petrolatum.121 However, caution is necessary in applying useful for the management of skin detachment and wounds povidone iodine over an extensive area in patients with around the anus. When it was used in 42 patients with fecal kidney or thyroid dysfunction or elderly patients because incontinence discharging liquid or semi-liquid stools, the of its absorption from the wound surface (iodine treatment was effective for maintaining or improving the poisoning).122 condition of the gluteal and perianal skin in 92% or more of

guide.medlive.cn Y. Yoshino et al.

patients even with risk factors of skin vulnerability.125 When Recommendation level: C1. 106 patients with perianal burns managed with the fecal Comments: diversion tube were compared with a previous 106 patients There are five RCT concerning hydrocolloid and two RCT managed without it, no significant difference was observed each concerning polyurethane film and hydrogel,129 and the in the mortality rate, but the incidences of subcutaneous evidence level is II for each. However, because no signifi- and urinary tract infections were reduced significantly from cant difference was observed in the time until cure com- 46.2% to 19.8% and from 27.4% to 14.2%, respectively, pared with oil-based ointments, the recommendation level and the treatment was also advantageous cost wise.123 was set at C1. In a prospective study in seven perianal burns and 13 with severe perianal excoriations, the severity score of perianal There is one case series study each concerning chitin and polyurethane foam,130,131 and the evidence level is V for skin damage was significantly reduced after intubation, the mean frequency of gauze change was reduced from 3.3 to each. 1.5 times/day, and the frequency of changes of bed linen While the use of alginate and Hydrofiber for second-degree burns is not covered by insurance, there is one RCT con- for patients with fecal incontinence was reduced from 9.3 to 129 1.2 times/day.126 In Japan, Nishibori et al. anally intubated cerning each, and the evidence level is II for both. How- five burn patients (three after surgery for gluteal burns and ever, as no significant difference was noted in the time until two with extensive burns) and reported that the treatment cure compared with silver sulfadiazine, the recommendation level was set at C1. was effective for defecation control with no wound contami- 127 nation. While the fecal diversion tube is recommended as SDB are usually not an indication for surgery and cure by a non-invasive treatment that should be considered before appropriate topical treatment. In DDB, a thin layer of necro- 126 ostomy, caution is needed as there have been reports of tic tissue is observed on the wound surface, but, if their area 128 anal ulceration and laxity, and lower gastrointestinal is limited, they are manageable by conservative treatment bleeding in patients receiving anticoagulant therapy the rela- after lysing the necrotic tissue by appropriate topical agents tionship of which with anal intubation cannot be or surgical debridement. Dressing materials are used for the 125 excluded. treatment of SDB and DDB after removal of necrotic tissue. Third-degree burns, which have thick necrotic tissue, are usually indications for surgery and not treated with dressing REFERENCES materials. 123 Echols J, Friedman BC, Mullins RF, et al. Clinical utility and eco- In the Cochrane review in 2008 concerning the effects of 129 nomic impact of introducing a bowel management system. J dressing materials on second-degree burns, 26 RCT Wound Ostomy Continence Nurs 2007; 34: 664–670. (evidence comparing various dressing materials with paraffin gauze or level III). silver sulfadiazine are mentioned. Among them, dressing 124 Donskey CJ. The role of the intestinal tract as a reservoir and materials available in Japan are evaluated in 11. Because source for transmission of nosocomial pathogens. Clin Infect Dis 2004; 39: 219–226. the dressing materials used in the remaining 15 trials are 125 Padmanabhan A, Stern M, Wishin J, Mangino M, Richey K, unapproved in Japan, they are excluded. The material DeSane M, Flexi-Seal Clinical Trial Investigators Group. Clinical referred to as paraffin in the Western published work is evaluation of a flexible fecal incontinence management system. comparable with a grease base such as white petrolatum Am J Crit Care 2007; 16: 384–393. (evidence level V). 126 Keshava A, Renwick A, Stewart P, Pilley A. A nonsurgical means used in Japan. While it is expressed as “oil-based ointment” of fecal diversion: the Zassi Bowel Management System. Dis Colon in the Remarks on recommendation, it is referred to as Rectum 2007; 50: 1017–1022. (evidence level IVa). “paraffin” in the Comments by respecting the original arti- 127 Nishibori A, Hiramatsu Y, Kato T, Kato Y, Asai S. Clinical evalua- cles. tion of a flexible fecal incontinence management system (FLEXI- â There are three RCT comparing hydrocolloid and paraffin 34 – SEAL ). J J Burn Inj 2008; : 284 289. (In Japanese) (evidence 129 level V). gauze in 236 patients. No significant difference was 128 Bordes J, Goutorbe P, Asencio Y, Meaudre E, Dantzer E. A non- observed in the time until cure compared with paraffin surgical device for faecal diversion in the management of perineal gauze in any of the reports. There are two RCT comparing – burns. Burns 2008; 34: 840 844. (evidence level V). hydrocolloid and silver sulfadiazine in 72 patients,129 and the time until cure did not significantly differ in one but was sig- TOPICAL TREATMENTS: DRESSING nificantly shorter with hydrocolloid in the other. MATERIALS Two RCT have been reported by the same authors concern- CQ20: ARE DRESSING MATERIALS USEFUL ing hydrogel.129 In these reports, data including those con- FOR THE TREATMENT OF SECOND-DEGREE cerning paraffin gauze and silver sulfadiazine are used as BURNS? controls, and the time until cure was shorter with hydrogel in both reports, but the difference was significant in one but Remarks on recommendation: Dressing materials such as not in the other. hydrocolloid, hydrogel, polyurethane film, chitin, polyurethane â There is one RCT comparing polyurethane film and paraffin foam, alginate and Hydrofiber are recommended as an option gauze in 55 patients,129 but the time until cure showed no for topical treatment for second-degree burns.

guide.medlive.cn The wound/burn guidelines – 6

significant difference. Also, there is an RCT comparing poly- materials, no evidence for recommending particular prod- urethane film and paraffin gauze saturated with chlorhexi- ucts among a large number of dressing materials is avail- dine, and the time until cure was significantly shorter with able. Therefore, dressing materials must be used by polyurethane film.129 Whether or not this difference was due understating their characteristics and considering the area to chlorhexidine is unclear, but the cure rate was higher with and site of the wound, presence or absence or risk of infec- polyurethane film until day 10, and the difference disap- tion, amount of effusion and age. Caution against wound peared thereafter. infection is also necessary, and, if the risk of wound infec- There is one each RCT concerning alginate and Hydrofiber tion is considered high, topical treatments other than a using silver sulfadiazine as a control, and neither showed a dressing material are recommended. difference in the time until cure.129 It must be noted that, in Japan, the use of alginate and Hydrofiber is covered by insurance only when they are applied to wounds reaching REFERENCES subcutaneous tissue. 129 Wasiak J, Cleland H, Campbell F. Dressings for superficial and Chitin has been used in Japan as a dressing material for partial thickness burns. Cochrane Database Syst Rev, 2008; 8: wounds including burns, but reports evaluating its effective- CD002106. (evidence level II). ness for the treatment of burns are few, and there is only 130 Beschitinâ Study Group in Kyusyu. Examination of usability of â one case series study in 120 patients including those with chitin dressing (Beschitin W) for wounds – multicenter clinical – donor site wounds and traumas.130 Of the 120 patients, 21 study in Kyusyu. Nishi J Dermatol, 1993; 55: 941 946. (evidence level V). had burns, and the treatment was effective or very effective 131 Nozaki M, Soejima K, Nakazawa H. Clinical application of lyofoam in 80% of them. However, the hemostatic and analgesic for the treatment of skin defects (pressure ulcers, burns and donor effects were included in the evaluation, and the effect on sites of split-thickness skin grafts), and the site of insertion of – wound healing is unclear. Also, there is no report evaluating tubes. Prog Med 1996; 16: 1101 1114. (evidence level V). 132 Ishibashi Y, Nakagawa H, Nakanishi H et al. Clinical study of Duo- the effectiveness of polyurethane foam exclusively for the DERM on skin ulcers. J Clin Therap Med 1986; 2: 1575–1584. (evi- treatment of burns, and there is only one case series study dence level V). in 150 patients including those with donor site wounds and 133 Ono I, Gunji H, Tateshita T, Kaneko F, Takiguchi Y. Examination of pressure ulcers.131 Of these patients, 35 had burns, and the usability of hydrocolloid covering material (HCD-02) for suture treatment was effective or very effective in 94% for improv- wound, burn and skin ulcer wound. Nishi J Dermatol 1996; 58: 319–329. (evidence level V). ing the condition of the wound surface. 134 Ueno T, Tsukada S, Heshiki T, Akaba N, Ihara E. Clinical trial While the reports in Japan on the use of dressing materials results of Hydrocel for donor sites and thermal burns. Nishi J Der- for the treatment of burns include those concerning hydro- matol 1998; 60: 206–211. (evidence level V). colloid,132,133 Hydrofiber134,135 and hydrogel,136,137 the effec- 135 Kishibe M, Kawakami S, Nozaki M et al. Clinical effects of car- boxymethylcellulose (AQUACELâ) for the treatment of dermal tiveness of the dressing material itself is evaluated in each burns. J J Burn Inj 2006; 32: 249–257. (evidence level V). report without comparing it with other treatments. 136 Aikawa N, Nozaki M, Takuma K et al. Clinical trial of hydrogel Of the studies on the effects of dressing materials in the dressing (NMD-101) on dermal burns, split-thickness skin donor management of second-degree burns mentioned in the sites, and skin defect injuries. Jpn Pharmacol Ther 2002; 30: 863– Cochrane review,129 six evaluated the incidence of wound 874. (evidence level V). 137 Kato T, Asai S, Hiramatsu Y, Nishihori A. Application of VIEWGEL infection. They consist of three RCT comparing hydrocolloid (a new hydrocolloidal dressing) on burn wounds. J J Burn Inj 2006; and paraffin gauze, one RCT comparing polyurethane 32:44–51. (evidence level V). film and paraffin gauze, one RCT comparing polyurethane film and paraffin gauze saturated with chlorhexidine, and TOPICAL TREATMENTS: TOPICAL AGENTS one RCT comparing silver-containing Hydrofiber and silver CQ21: WHAT TOPICAL AGENTS SHOULD BE sulfadiazine, and they are in agreement in that there was no USED FOR THE TREATMENT OF SECOND- significant difference in the incidence of wound infection DEGREE BURNS? between the trial and reference materials. In the Cochrane review,129 eight RCT evaluated the fre- Remarks on recommendation: For the initial treatment of sec- quency of dressing changes. The frequency of changes was ond-degree burns, ointments with oleaginous bases such as reported to be higher with the dressing material in one but petrolatum, zinc oxide and dimethyl isopropylazulene are rec- to be lower compared with paraffin gauze or silver sulfadi- ommended as an option (C1). azine in six and not to be different in one. For second-degree burns, trafermin, tretinoin tocopherol, For dressing materials to sufficiently function as a preserver bucladesine sodium and prostaglandin E1 are recommended of an appropriate moist environment or a barrier against (B). bacterial infection, they must be in close contact with the Lysozyme hydrochloride, aluminum chlorohydroxy allan- normal skin around the wound. Actually, however, as it is toinate (Alcloxa) and so forth are recommended as an option difficult to apply a dressing material over a wide area, and (C1). as there is a cost restriction, dressing materials are used for For chronic ulcers accompanied by necrotic tissue resulting the treatment of relatively small burns that can be covered from DDB, the use of bromelain ointment, cadexomer iodine, with them. Because there is no RCT comparing dressing

guide.medlive.cn Y. Yoshino et al.

dextranomer and silver sulfadiazine is recommended as an RCT comparing it with bendazac in patients with various option for the removal of necrotic tissue (C1). skin ulcers including those due to burns145 and one case Recommendation level: B and C1. series study in patients with ulcers due to burns,146 and the Comments: evidence level is II and V, respectively. However, the recom- For chronic ulcers caused by burns, topical agents should mendation level of the former was set at C1 because of the be selected for wound bed preparation based on the TIME lack of detailed description about the burns. Regarding alu- concept or moist wound healing. It is also important to minum chlorohydroxy allantoinate, there is a double-blind appropriately select not only the principal agent but also the RCT comparing it with the base in 62 patients with skin base according to the condition of the wound surface. The ulcers including those due to burns, erosion, eczema and following topical treatments are recommended by the dermatitis,147 but the recommendation level was set at C1, Guidelines for the Management of Pressure Ulcers as topical because there was no detailed description or evaluation agents appropriate for wound bed preparation, but the topi- about the burns. cal agents used for T (removal of necrotic tissue) and M In second-degree burns, damage of the dermis is partial, (maintenance of the moist environment) in burns are the and the selection of topical agents in consideration of not same: only the antibacterial action but also wound healing is necessary. The principle of topical treatment for wounds in gen- T (removal of necrotic tissue): Cadexomer iodine, silver eral converges on protecting the wound surface and sulfadiazine, dextranomer, bromelain ointment. 148 maintaining a moist environment. However, as it is diffi- I (control/elimination of infection): Cadexomer iodine, silver cult to accurately determine the depth of burns early after sulfadiazine. injury, and as burns ranging from first-degree burns to DDB M (maintenance of the moist environment): When effusion is are often mixed, topical agents to be used are difficult to excessive, cadexomer iodine, dextranomer and bucladesine specify. Therefore, oil-based ointments may be used in the sodium; when effusion is deficient, aluminum chlorohydroxy stage of initial treatment, but topical agents appropriate for allantoinate, ointments containing antibiotics (antibacterial the condition of the wound surface must be selected as it agents), tretinoin tocopherol, prostaglandin E1, lysozyme becomes clear. hydrochloride and ointments with a oil base such as petro- Ointments containing antibiotics (antibacterial agents) are latum. oil-based ointments. While they may be used for the protec- E (management of wound edges): No recommendable topi- tion of the wound surface and maintenance of the moist cal agents. environment, their use should be restricted to a short period, Concerning the use of oil-based ointments for second- because their long-time use may invite the development of degree burns, there is only an expert opinion,138 and the resistant bacteria. evidence level is VI. There is one RCT showing the effective- Akita et al. performed an RCT by randomizing 102 adults ness of trafermin for the treatment of second-degree with second-degree burns into trafermin and non-trafermin 139 burns,139 and the evidence level is II. Regarding tretinoin groups. As a result, they reported that the time until cure tocopherol, there is one double-blind RCT comparing it with was significantly shorter in the trafermin group and that the bendazac in patients with various skin ulcers including those elasticity and hardness scores of the scar and moisture- caused by burns140 and one non-blinded RCT comparing it retaining ability were all significantly higher in the trafermin with lysozyme hydrochloride,141 and the evidence level is II. group compared with a control group consisting of 51 However, no details such as the depth of the burns are pro- healthy volunteers. Komuro et al. evaluated 32 patients (in- vided. Concerning bucladesine sodium, there is one double- cluding children) with second-degree burns conservatively blind RCT each comparing it with the base and lysozyme treated using trafermin, comparing those administrated the hydrochloride in patients with various skin ulcers including drug within 3 days and after 4 days or more after injury, and those caused by burns,142,143 and the evidence level is II. reported that the mean number of days until epithelialization However, no detailed description concerning the burns is and cumulative cure rate were both statistically superior in 149 provided. As for prostaglandin E1, there is a non-blinded the group treated within 3 days. Fujiwara et al. evaluated RCT comparing it with lysozyme hydrochloride in patients 20 patients with fresh second-degree burns in whom treat- with various skin ulcers including those due to burns,144 and ment was initiated within 48 h after injury by comparing the evidence level is II, but no detailed information including those treated with trafermin and those treated with white the depth is provided about the burns, and the number of petrolatum alone and reported that the number of days until patients is small. However, as tretinoin tocopherol, buclade- epithelialization was significantly shorter in the trafermin 150 – sine sodium and prostaglandin E1 are rated similarly to group. Also, Shiozawa et al. performed a case control trafermin in the Guidelines for the Management of Pressure study comparing 171 patients with DDB (including infants Ulcers, which are similar chronic skin lesions, the recom- and children) treated with trafermin and 53 historical con- 151 mendation levels of these topical agents were determined trols conservatively treated without trafermin and reported similarly to trafermin on the basis of consensus of the com- that patients who showed hypertrophic scarring were signifi- mittee. Concerning lysozyme hydrochloride, there is one cantly fewer in the trafermin group.

guide.medlive.cn The wound/burn guidelines – 6

Trafermin is a spray type liquid preparation, and it must be dermatitis,147 and reported that the efficacy rate in all used with some topical agents or dressing material to main- patients was significantly higher in the true drug group, but tain a moist environment for burns. Recently, there have the number of patients with each disorder was small, and been reports of the concomitant use of artificial dermis and no statistical evaluation of individual disorders including burn intra-bulla injection,152,153 but no established method has was performed. been proposed concerning the selection of the topical If ulcers accompanied by necrotic tissue have developed as agents or dressing materials to be used with these treat- a result of DDB, topical agents should be selected from the ments. above after surgical debridement. If the general condition is A double-blind RCT comparing tretinoin tocopherol and poor, or if the necrotic tissue is thin, and surgical debride- bendazac has been performed in 152 patients with various ment cannot be performed, topical application of bromelain, skin ulcers including 44 with ulcers due to burns by the L- silver sulfadiazine, cadexomer iodine or dextranomer for the 300 Clinical Trial Group.140 While there is no mention of the removal of necrotic tissue should be considered (see CQ23). depth of burns or time after injury, granulation 1 week after the application of the test drugs was reported to be significantly better in the tretinoin tocopherol group. There is also REFERENCES a unblended RCT comparing tretinoin tocopherol and lyso- 138 Kamiya T, Ono I. A practical concept of topical therapy in burn zyme hydrochloride in 217 patients with various skin ulcers wound (moist wound care). MB Derma 2008; 146:21–28. (evidence including 36 with ulcers due to burns, but no detailed level VI). description is provided concerning the depth of burns or 139 Akita S, Akino K, Imaizumi T, Hirano A. Basic fibroblast growth fac- time after injury, and no significant difference was reported tor accelerates and improves second-degree burn wound healing. – to be observed in the ulcers due to burns between the two Wound Rep Reg 2008; 16: 635 641. (evidence level II). 141 140 Clinical Research Group for L-300. Clinical evaluation of L-300 groups. ointment in the treatment of skin ulcers – controlled comparative Shinmura et al. performed double-blind RCT comparing study by using Bendazac ointment as a control. J Clin Therap bucladesine sodium and the base in 150 patients with pres- Med, 1991; 7: 437–456. (evidence level II). sure ulcers/skin ulcers including 20 with ulcers due to burns 141 Clinical Research Group for L-300. Clinical evaluation of L-300 ointment in the treatment of skin ulcers – controlled comparative and comparing bucladesine sodium and lysozyme study by using Lysozyme chloride ointment. J Clin Therap Med, hydrochloride in 275 patients with pressure ulcers/skin 1991; 7: 645–665. (evidence level II). ulcers including 40 with ulcers due to burns.142,143 Accord- 142 Niimura M, Yamamoto K, Kishimoto S et al. Clinical evaluation of ing to these reports, bucladesine sodium was significantly DT-5621 in patients with chronic skin ulcer – multicenter, placebo- – superior in the ulcer area reduction rate, granulation and controlled double blind study. Jpn Pharmacol Ther 1990; 18: 245 258. (evidence level II). epithelialization, but no detailed information is provided con- 143 Niimura M, Ishibashi Y, Imamura S et al. Clinical study of Dibutyryl cerning the depth of burns or time after injury. There is, cyclic AMP ointment (DT-5621) in chronic skin ulcers – well-con- however, a report that the blood concentration of buclade- trolled comparative study with Lysozyme ointment. J Clin Therap – sine sodium increased and remained elevated for a period Med 1991; 7: 677 692. (evidence level II). 144 Imamura S, Sagami S, Ishibashi Y et al. Clinical study of prosta- after its topical application,154 so attention to the general glandin E1 ointment (G-511 ointment) in chronic skin ulcers – well- condition including the blood pressure, urine volume and controlled comparative study with Lysozyme chloride ointment. J blood glucose level is necessary when it is topically applied Clin Therap Med 1994; 10: 127–147. (evidence level II). to a wide area. 145 Study Group for KH-101. Clinical evaluation of KH-101 ointment – Imamura et al. performed a non-blinded RCT comparing (Reflap ointment) in skin ulcers new analysis of well controlled comparative study. Nishinihon Derma, 1986; 48: 553–562. (evi- prostaglandin E1 and lysozyme hydrochloride in 171 dence level II). patients with pressure ulcer/skin ulcer including 26 with 146 Kawakami S, Tsukada S, Nanba K et al. The effect of Lysozyme ulcers due to burns.144 According to their report, there is no ointment for the treatment of dermal burn wounds. J J Burn Inj – detailed mention of the depth of burns or time after injury, 1989; 15: 109 117. (evidence level V). 147 Konjiki S. Clinical evaluation of Alkisa ointment in the treatment of but the efficacy rate in ulcers due to burns was significantly skin disease – double blind controlled study. Jpn Pharmacol Ther higher in the prostaglandin E1 topical application group. On 1977; 5: 172–176. (evidence level VI). the other hand, no significant difference was observed in 148 Hinman CD, Maibach H. Effect of air exposure and occlusion on the ulcer area reduction rate between the two groups. experimental human skin wounds. Nature 1963; 200: 377–378. Kawakami et al. performed a case series study using lyso- 149 Komuro A, Kishibe M, Yamamoto Y et al. Treatment for second- degree burn wounds using Trafermin (Fiblastâ spray). J J Burn Inj zyme hydrochloride in 28 patients with SDB and 40 with 2009; 35:27–39. (evidence level III). 146 DDB. In this study, the improvement of all second-degree 150 Fujiwara O, Soejima K, Nozaki M et al. Treatment of acute second burns was greater in the lysozyme hydrochloride group, but degree burn wound with bFGF. J J Burn Inj 2008; 34:29–37. (evi- granulation was suggested to become excessive, and dence level III). 151 Shiozawa K, Mukae N, Nishimura G. Inhibition of hypertrophic epithelialization to be delayed, in patients with old (topical scars by administration of basic fibroblast growth factor. Jpn J application initiated ≥5 days after injury) DDB. Plast Surg 2009; 52: 543–549. (evidence level IVb). Konjiki carried out a double-blind RCT comparing aluminum 152 Mitsukawa N, Suse T, Karube D et al. Clinical study of treatment chlorohydroxy allantoinate and the base in 62 patients with skin defects using a combination of artificial dermis and bFGF – skin ulcers including those due to burns, erosion, eczema or preparation. Jpn J Plast Surg 2009; 52: 517 527.

guide.medlive.cn Y. Yoshino et al.

153 Kurokawa M, Morooka H, Jinno C. Treatment for partial thickness but not at a sufficient concentration.161 Also, in extensive burns with Intra-bleb bFGF infusion therapy and hydrogel covering burns with a large amount of exudates, silver sulfadiazine is therapy following bFGF spray. J J Burn Inj 2009; 35:21–26. reported to be inactivated with a marked decrease in its 154 Ito Y, Aoyama H, Yokoo K et al. Absorption of Bucladesine sodium 162 ointment from burn wounds. J J Burn Inj 1998; 24:13–21. effect. Therefore, repeated applications should be considered under such circumstances. Because an emulsion base is used in silver sulfadiazine CQ22: IS SILVER SULFADIAZINE USEFUL FOR preparations, they have high tissue permeability and are THE TREATMENT OF EXTENSIVE THIRD- expected to produce a debriding effect by promoting autoly- DEGREE BURNS? sis of necrotic tissue (see CQ23). Remarks on recommendation: Silver sulfadiazine is recom- As adverse effects of silver sulfadiazine, leukocytopenia, mended for the treatment of extensive third-degree burns. methemoglobinemia, silver deposition, allergic reaction to Recommendation level: B. sulfonamides and so forth have been reported. Sufficient Comments: attention to these adverse effects is considered necessary, Concerning the topical use of silver sulfadiazine for the particularly when silver sulfadiazine is topically applied to treatment of third-degree burns, there are two non-rando- extensive burns. However, leukocytopenia is also occasion- mized comparative trials,155,156 and the evidence level is III. ally observed in the use of other drugs, and there is the opin- The primary objective of topical agents for extensive third- ion that it should not be regarded as a side-effect specific to 163 degree burns is to prevent infection from the wound surface silver sulfadiazine. There is also the opinion that the use of until surgical debridement. Silver sulfadiazine is widely used silver sulfadiazine should be avoided as much as possible for in Japan and abroad for the treatment of burns, and there wounds showing active proliferation of epidermal keratinized are multiple reports indicating an excellent antibacterial cells such as donor site wounds and SDB, because the cyto- 161 action. Also, as it is convenient for application to a wide toxicity of silver delays wound healing. area because of the emulsion base, its recommendation level was set at B. Pegg et al. performed a non-randomized comparative trial in REFERENCES patients with burns of various degrees by treating 314 with 155 Pegg SP, Ramsay K, Meldrum L, Laundy M. Clinical comparison of silver sulfadiazine, 156 with maphenide (unmarketed in maphenide and silver sulfadiazine. Scand J Plast Reconstr Surg Japan), and 175 historical controls with gentamycin sulfate 1979; 13:95–101. (evidence level III). 155 and so forth, and reported that the mortality rate, positive 156 Ohyama K. Clinical comparison of silver sulfadiazine cream (T-107) rate of bacterial cultures, and detection rates of P. aerugi- and Gentamycin ointment in burn wound. J J Burn Inj 1980; 6:87– nosa, staphylococci, Proteus and Candida were significantly 96. (evidence level III). 157 Ono I, Ohura T, Manabe M et al. Topical therapy on burned reduced in the silver sulfadiazine group compared with the patients – comparison with silver sulfadiazine cream and other control and maphenide groups. In Japan, Oyama et al. car- ointment. J J Burn Inj 1982; 8:3–12. (evidence level VI). ried out a non-randomized comparative trial evaluating the 158 Yura J, Andoh M, Ishikawa S. Clinical evaluation of silver sulfadi- effects of silver sulfadiazine and gentamycin sulfate in 31 azine (T107) in decubitus, chronic skin ulcers – comparison with placebo by a double blind method. Chemotherapy 1984; 32: 208– patients with moderate to severe burns according to Artz’s 156 222. criteria, and reported that silver sulfadiazine was mark- 159 Heggers JP, Robson MC. The emergence of silver sulphadiazine- edly effective against Klebsiella, Serratias, other Gram-nega- resistant Pseudomonas aeruginosa. Burns 1979; 5: 184–187. tive bacteria and Candida. 160 Li XZ, Nikaido H, Williams KE. Silver-resistant mutants of Escheri- + Ono et al. evaluated the minimum inhibitory concentrations chia coli display active efflux of Ag and are deficient in Silver Sul- fadiazine. J Bacteriol 1997; 179: 6127–6132. (evidence level VI). (MIC) of various antibacterial agents against P. aeruginosa, 161 Atiyeh BS, Costagliola M, Hayek SN, Dibo SA. Effect of silver on because its detection rate increases with time among bacte- burn wound infection control and healing review of the literature. ria isolated from burns. As no strain resistant to silver sulfa- Burns 2007; 33: 139–148. (evidence level V). diazine or maphenide was observed, they recommended 162 Hoffmann S. Silver sulfadiadine: an antibacterial agent for topical use in burns. Scand J Plast Reconstr Surg 1984; 18: 119–126. (evi- them as topical antibacterial agents for burns.157 Also, Yura dence level V). et al. performed resistance-acquisition and bactericidal 163 Frederick W. The side effect of silver sulphadiazine. J Burn Care studies using silver sulfadiazine against P. aeruginosa and Res 2009; 30: 464–470. (evidence level V). reported infrequent development of resistance and a satis- 158 factory bactericidal action of the drug. On the other hand, CQ23: WHAT TOPICAL AGENTS SHOULD BE there have been reports of infections resistant to silver 159 USED TO REMOVE NECROTIC TISSUE FROM preparations including silver sulfadiazine. According to SMALL THIRD-DEGREE BURNS? the report by Li et al.,160 bacteria are shown to acquire resistance to silver in the presence of silver at a low concen- Remarks on recommendation: As topical agents aimed to tration, and Atiyeh et al. suggested the necessity to maintain remove necrotic tissue from small third-degree burns, brome- an appropriate silver concentration at the wound, because lain, cadexomer iodine, dextranomer and silver sulfadiazine are resistance to silver develops at concentrations near the MIC recommended as an option.

guide.medlive.cn The wound/burn guidelines – 6

Recommendation level: C1. its permeation characteristics.171 However, there are a few Comments: points that need attention in its use: it may cause edema on Concerning bromelain, there is one RCT evaluating its the wound surface in wounds rich in effusion, its effect is debriding effect on third-degree burns,164 and the evidence attenuated when it is used with povidone iodine, and its level is II. However, as its effect was similar to those of concomitant use with other drugs, particularly topical cuta- other drugs and attenuated in dried wounds, the recommen- neous enzyme preparations, should be avoided.165 dation level was set at C1. Regarding dextranomer and cadexomer iodine, there are non-randomized comparative trials in patients with various REFERENCES skin ulcers including ulcers due to burns,165,166 and a case 167 164 Anzai T, Tomizawa T, Muramatsu T et al. Effect of Bromelain oint- series study, and the evidence level is III and V, respec- ment in necrotic tissue. Jpn J Plast Surg 1972; 15: 456–462. (evi- tively. In these reports, the response rate with the debriding dence level II). effect included was high, but burns were not focused, and 165 Asada Y, Higashida T, Odaka T et al. Clinical efficacy of NI-009 in the number of patients was small. Both of these drugs are various cutaneous ulcers (phase III study). J Clin Therap Med 1990; 6: 101–117. (evidence level V). indicated for wounds rich in effusion, and caution is needed 166 Japanese Society of Pressure Ulcers “Pressure Ulcer in their use for wounds deficient in effusion, because they Prevention and Control Guideline” Development Committee. may cause drying of the wound surface and delay wound Removal of Necrotic Tissue for N to n. 2009; 107–113. (evidence healing.168 level VI). For silver sulfadiazine, there is no report evaluating the 167 Tachibana T, Miyachi Y. Conservative treatment by drug. Jpn J Plast Surg 2003; 46: 459–470. (evidence level II). debriding effect except for expert opinions about pressure 168 Study Group for SK-P-9701. Clinical study results of SK-P-9701 166,167 ulcers, and the evidence level is VI. However, there (Dextranomer paste) in various cutaneous ulcers. J Clin Therap has been rich experience in the clinical use of silver sulfadi- Med, 2000; 16: 1419–1437. (evidence level III). azine, and it is also expected to have a preventive effect 169 Suetsugu T, Yashiro A, Yamasaki R et al. Clinical efficacy of Sol- coseryl ointment in burn. The Clinical Report 1975; 9: 2433–2452. against infection (see CQ22). (evidence level II). As for the ointment containing calf blood extract, there is 170 Ogawa Y, Kurooka S, Katakami S et al. The evaluation of the effect one RCT indicating its usefulness for the treatment of third- of Bromelain ointment on the debridement of eschar of burn, decu- degree burns,169 and the evidence level is II. However, as bitus and various wound. J New Rem Clin 1999; 48:69–77. (evi- this preparation was manufactured and approved in 1963 dence level V). 171 Kukita A, Ohura T, Aoki T et al. Clinical evaluation of NI-009 on and has recently been used rarely, it was excluded from the various cutaneous ulcers – comparative study with Elaseâ-C oint- evaluation for recommendation. ment. J Clin Therap Med 1990; 6: 817–848. Regarding the debriding effect of fradiomycin sulfate/crys- talline trypsin, there are only expert opinions, and the evi- CQ24: ARE TOPICAL STEROID dence level is VI. As this preparation was also manufactured PREPARATIONS USEFUL FOR THE and approved in 1962 and has recently been used rarely, it TREATMENT OF FIRST-DEGREE BURNS AND was excluded from the evaluation for recommendation. SDB? Anzai et al. performed an RCT using bromelain and placebo prepared by mixing inactivated bromelain with the same Remarks on recommendation: The use of topical steroid base in 33 patients with deep second-degree or third- preparations is recommended as an option in expectation of degree burns (7–10 days after injury).164 They separated the their anti-inflammatory effects. wound of each patient into halves, applied the true drug or Recommendation level: C1. placebo topically to each half, and compared the degree of Comments: lysis of necrotic tissue, hemorrhage and pain, reporting that There are only expert opinions concerning the usefulness of the true drug showed a significantly greater debriding effect topical steroid preparations for the treatment of burns,172–174 in third-degree burns. There are many other case reports and the evidence level is VI. On the other hand, there are indicating the usefulness of bromelain. Ogawa et al. evalu- three RCT (including double-blind trials) suggesting that ated the debriding effect of bromelain in ulcer patients topical steroid preparations showed no anti-inflammatory including 28 with ulcers due to burns and reported that a effect on the skin that has sustained physical damage response rate of 86% was obtained in ulcers due to including burn.175–177 However, we noted that expert opin- 170 burns. In using bromelain, attention to pain, which occurs ions suggesting the usefulness of topical steroid prepara- frequently, is necessary. Also, as highly water-absorbing tions for the treatment of first- or second-degree burns are macrogol is used as the base, its debriding effect is attenu- predominant and that topical steroid preparations have been ated when effusion or the moisture of the wound surface is used widely for the treatment of burns in Japan. 168 reduced. Yamanaka et al. recommend the use of a very strong or Silver sulfadiazine is considered to produce a wound sur- even stronger topical steroid preparation for first-degree face cleaning effect as its emulsion base with high water burns for a short period from immediately after injury to content causes softening and lysis of necrotic tissue due to rapidly repair damaged tissue and control inflammation.172

guide.medlive.cn Y. Yoshino et al.

Takuma et al. recommend the use of topical steroid prepa- more. They also treated one group by using gentamycin sul- rations for areas of first-degree burns with marked redden- fate after topical application of betamethasone valerate/gen- ing/pain.173 Hitoshi et al. reported that the use of topical tamycin sulfate for 3 days but another group by using steroid preparation should be restricted to the first 2 days gentamycin sulfate alone from the beginning and observed after injury in first- or second-degree burns, because they no significant difference in the comprehensive evaluation of delay wound healing and suppress epithelialization while objective findings, number of days until completion of they are very effective for suppressing reddening and edema epithelialization or overall pharmacological effect. and mitigating pain in the acute period.174 Pederson et al. however, performed a double-blind RCT by artificially creating first-degree burns or SDB in healthy vol- REFERENCES unteers and compared the anti-inflammatory effect between 172 Yamanaka K, Mizutani H. Princple of initial treatment in burn clobetasol propionate and placebo according to the severity wound. MB Derma 2008; 146:16–20. (evidence level VI). of pain and erythema and reported no significant difference 173 Taguma K, Sasaki J. 9 Treatment and topical therapy, BURN – between the two groups.175 Faurschou et al.176 examined index of initial treatment and topical therapy antibacterial chemotherapy in burn. Med J, 2008; 129–156. (evidence level VI). the effects of an topical steroid preparation on sun burn (ul- 174 Todoroki T, Okano Y, Moriuchi H. From daily inquiry – adrenal cor- traviolet B irradiation) in 20 healthy volunteers but observed ticosteroid. J Pract Pharm 1988; 39: 1085–1093. (evidence level no clinical usefulness when it was applied after irradiation. VI). Also, Matsumura et al. carried out a double-blind trial con- 175 Pedersen JL, Moiniche S, Kehlet H. Topical glucocorticoid has no cerning the effects of betamethasone valerate/gentamycin antinociceptive or anti-inflammatory effect in thermal injury. Br J Anaesth 1994; 72: 379–382. sulfate on fresh second-degree burns using gentamycin sul- 176 Faurschou A, Wulf HC. Topical corticosteroids in the treatment of 177 fate as a control drug. According to this study, no differ- acute sunburn a randomized, double-blind clinical trial. Arch Der- ence was observed in the alleviation of swelling or pain matol 2008; 144: 620–624. between the two groups, and betamethasone valerate/gen- 177 Muramatsu T, Sekiguchi T. The clinical use of corticosteroid ointment for acute second degree burn. Jpn J Plast Surg 1972; 15: tamycin sulfate promoted epithelialization until 2 days from 318. the beginning of their use but suppressed it after 4 days or

guide.medlive.cn